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BASF Pharma Ingredients Generic Drug Formulations 2005

2 Tablets obtainedby direct compression

2.1 Size of formulations

The formulations were developed ona laboratory scale in which case200 –1,000 g of the mixtures to be tabletted were used. Normally, theamounts weighed out in the formula-tions correspond to the amount in thetablets multiplied by a factor of 1,000.

2.2 Direct compression

The technology involved in directcompression assumes great impor-tance in the tablet formulations, be-cause it is often the cheapest means,particularly in the production of ge-nerics, that the active substance per-mits. The limiting factors are thephysical properties of the active sub-stance and its concentration in thetablets (cf. Chapter 2.4). Even sub-stances such as ascorbic acid thatare hardly suitable for direct compres-sion, owing to the friability of theircrystals, can normally be directlypressed into tablets at concentrationsof 30 – 40 %. However, this techniqueis not as suitable if the content of as-corbic acid is higher. This limit may beshifted upwards by special directcompression auxiliaries, e.g. Ludi-press. Two important alternatives, viz.Ludipress grades and Kollidon VA 64,can be found in the BASF line ofpharmaceutical excipients for directcompression.

A. Ludipress grades

Ludipress is a speciality derived fromlactose, Kollidon 30, and Kollidon CL.It thus combines the properties of afiller, binder, disintegrant, and flowagent and also often acts as a releaseaccelerator. By virtue of its versatility,formulations containing it are usuallyvery simple. It can also be combinedwith almost all active substances withthe exception of those that enter intoa chemical interaction with lactose(Maillard reaction).

Active substances, e.g. many anal-getics, behave very differently withLudipress when the dosage is ex-tremely high. Acetylsalicylic acid andmetamizole can be pressed when little Ludipress has been added; ibuprofen requires a larger amount;and the fraction of Ludipress requiredin the tablets is too large for para-cetamol (= acetaminophen).

B. Kollidon VA 64

An alternative to the Ludipress gradesis the outstanding dry binder KollidonVA 64 together with excipients, e.g.calcium phosphate, microcrystallinecellulose, lactose, or starch, and adisintegrant, e.g. Kollidon CL. Thiscombination even allows 500 mg ofparacetamol to be pressed into goodtablets with a weight of 700 mg.

No other dry binder has a bindingpower and plasticity comparable tothose of Kollidon VA 64. Plasticity, inparticular, is an important parameterin direct compression. As can beseen in Fig. 1, this property of Kolli-don VA 64 is not adversely effectedby increasing the pressure. The bene-ficial properties of Kollidon VA 64 can

129738_Rezeptblaetter.qxd 07.06.2005 10:57 Uhr Seite 25


also be exploited for the productionof concentrated active substance thatis subsequently used for direct tablet-ting.

Obviously, Kollidon VA 64 and Ludi-press can also be combined with oneanother.

2.3 Tablet press

All the formulations were devised onrotary tabletting presses that were fitted with 10 – 20 punches.

2.4 Effect of the physical prop-erties of the active substance

In the manufacture of tablets it isimportant to define and appreciatethe physical properties of the activesubstance. This particularly concernsthe particle size and the flowability.

Fig. 2 shows the difference that canoccur when ascorbic acid tablets ofthe same composition are producedat the same pressure, but when theactive substance consists of crystalsof two different sizes (crystalline = > 150 µm; powder = < 150 µm).

2.5 Effect of the physical properties of the excipients

Characterization of the physical prop-erties of excipients is also importantbecause the influences can be similaras mentioned for active ingredients.

2.6 Methods of measuring theproperties of tablets

The general instructions for the deter-mination of the corresponding proper-ties of tablets (hardness, disintegra-tion, friability, dissolution) are con-tained the Pharmacopoeiae Ph.Eur. orUSP. If it is not stated to the contrary,the disintegration time is measured in

Fig. 1 Plasticity of dry binders in tablets(99.5 % binder + 0.5 % magnesium stearate)

1.0

0.9

0.8

0.7

0.6

0.4

0.5

Kollidon VA 64 Kollidon 30 Mc. Cellulose HPMC 11000

Pla

stic

ity

Plasticity = plastic energy/total energy

Force: 18 kN

Force: 25 kN



artificial gastric juice. The dissolutionis determined by the conditions laiddown in the corresponding mono-graphs for the tablets (usually USP)and in the prescribed medium.

2.7 Information on dissolution ofactive substance

Nowadays it is standard practiceand/or laid down that the in-vitro release of active substance bechecked. Unfortunately, these datacannot be given for all formulations.This is particularly the case when theactive substance is sufficiently solubleor when the formulation was devel-oped in a time when this parameterwas not yet demanded.

2.8 Formulations

The formulations in this chapter havebeen arranged in the alphabetic orderof their active substances.

140

120

100

80

40

60

crystalline gradeCompression force: 25 kN

powder grade

Tabl

et H

ardn

ess

(N)

Fig. 2 Direct compression of different types of ascorbic acid(40 % ascorbic acid, 5 % Kollidon VA 64)


Acetylcysteine Effervescent Tablets (600 mg)

Formulation

Acetylcysteine, crystalline (Merck).............600 gLudipress LCE [1] ....................................400 gSodium bicarbonate ................................450 gTartaric acid, powder ...............................350 gPolyethylene glycol 6000, powder [6]..........75 gApartame (Searle) ......................................25 gOrange flavour (Dragoco) ............................q.s.

2. Manufacturing (Direct compression)

Mix all components, pass through a sieve and press with medium com-pression force at a maximum of 30 % of relative atmospheric humidity.

3. Tablet properties

Weight................................................1975 mgDiameter ...............................................20 mmForm ...................................................biplanarHardness..................................................97 NDisintegration......................................2 – 3 minFriability ...................................................1.1%


2.8 Formulations of Tablets Obtained by Direct Compression (Lab Scale)


Acetylsalicylic Acid + Paracetamol (= Acetaminophen) + Caffeine Tablets (400 mg + 100 mg + 30 mg)

Formulation

Acetylsalicylic acid, crystalline ..................400 gParacetamol, crystalline (BASF) ................100 gCaffeine (BASF) .........................................30 gLudipress [1] ...........................................100 gKollidon CL [1] ..........................................20 gPolyethylene glycol 6000, powder [6]..........30 gStearic acid [7] ............................................5 g


Mix all components, pass through a sieve and press with low compres-sion force.


Weight .................................................683 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness ................................................116 NDisintegration......................................1 – 2 minFriability...................................................0.3 %




Acetylsalicylic Acid-Acetaminophen-Caffeine-Tablet (250 mg +250 mg+ 50 mg)

Formulation

Acetaminophen powder ........................250.0 gCaffeine powder .....................................50.0 gASS powder .........................................250.0 gKollidon® VA 64 ....................................60.0 g

b) Manufacture by Roller Compaction

The active ingredients and Kollidon® VA 64 were granulated in a Gerteis Roller compactor.

Process parameters

Force ...............................................5.0 kN/cmCrack...................................................2.9 mmLooser .................................................5.0 rpmDosing srew .......................................90.5 rpmPlug screw .......................................108.6 rpmGranulator.............................................50 rpm

c) Formulation of the tablets

Acetaminophen powder .....................250.0 mgCaffeine powder ..................................50.0 mgASS powder ......................................250.0 mgKollidon® VA 64 ..................................60.0 mgKollidon® CL.......................................20.0 mgAerosil 200 ............................................3.0 mgMagnesium stearate [8] ..........................4.0 mg


2. Formulations of Tablets Obtained by Direct Compression (Lab Scale)


d) Tableting

The granules were passed together with magnesium stearate, Aerosil® 200 and Kollidon® CL through an 800µm sieve, blended for 10 min in a Turbula mixer and compressed into tablets with a forceof about 12kN.

Tablet press ..................Korsch PH106, 30 rpmCompression force ................................11.5kN

e) Tablet properties

Weight ...............................................629.7mgS rel ........................................................1.4 %Diameter ................................................12mmForm ...................................................biplanarHardness...................................................72NFriability.................................................2,75 %

f) Dissolution


Acetylsalicylic Acid-Acetaminophen Caffeine-Tablet (250 mg +250 mg+ 50 mg) page 2

0

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120

0 20 40 60 80 100 120 140

time [min]

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BASF

Melabon

method: paddle 50 rpm; 37°Cdeionized water


g Content uniformity


Acetylsalicylic Acid-Acetaminophen Caffeine-Tablet (250 mg +250 mg+ 50 mg) page 3

175,00

200,00

225,00

250,00

275,00

300,00

325,00

0 1 2 3 4 5 6 7 8 9 10

number of tablets

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t [m

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130

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]

assay

experial content


Acetylsalicylic Acid + Paracetamol (= Acetaminophen) Tablets(250 mg + 250 mg)

Formulation

Acetylsalicylic acid, crystalline (Merck) ......250 gParacetamol, crystalline (BASF) ................250 gAvicel PH 101 [5] .......................................60 gKollidon 30 (or Kollidon VA 64) [1] ...............15 gKollidon CL [1] ..........................................25 g


Pass all components through a 0.8 mm sieve, mix and press withmedium compression force.


Weight .................................................605 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................90 NDisintegration .......................................< 1 minFriability...................................................0.7%

4. Chemical stability of formulation No. 2 (20–25 °C, closed)

0 Months 6 Months 12 Months

Acetylsalicylic acid 100 % 100 % 100 %Vitamin C 100 % 100 % 96 %Free acetic acid < 0,01% < 0.01%Free salicylic acid < 0,01% < 0.01%




Acetylsalicylic Acid + Vitamin C Effervescent Tablets (400 mg + 250 mg)

1. Formulations

No. 1 No. 2

Acetylsalicylic acid (Synopharm) ....................400 g 400 gAscorbic acid, crystalline (BASF) ...................250 g 250 gLudipress LCE [1] .........................................600 g 500 gCtitric acid, crystalline ..................................300 g 400 gSodium bicarbonate .....................................600 g 600 gLutrol E4000F [1]............................................90 g 90 g


Pass all components through a 0.8 mm sieve, mix and press with highcompression force.


No. 1 No. 2

Weight ....................................................2251 mg 2244 gDiameter ....................................................20 mm 20 mmForm ........................................................biplanar biplanarHardness.....................................................145 N 125 NDisintegration ....................................1 min 35 sec 1 min 22 secFriability .....................................................0.66 % 0.86 %Colour ..........................................................white white




Acetylsalicylic Acid + Vitamin C Tablets (325 mg + 250 mg)

1. Formulations

No. 1 No. 2

Acetylsalicylic acid, crystalline (Merck) ...........325 g 325 gAscorbic acid, powder (BASF).......................250 g 250 gSorbitol, crystalline [10] .................................120 g –Avicel PH 101 [5] ............................................40 g 100 gKollidon VA 64 [1] ...........................................25 g 12 gKollidon CL [1] ...............................................20 g 30 gMagnesium stearate [2] ....................................2 g 3 g


Pass all components through a 0.8 mm sieve, mix and press withmedium/high compression force.


No. 1 No. 2

Weight ......................................................790 mg 726 mgDiameter ....................................................12 mm 12 mmForm ........................................................biplanar biplanarHardness ......................................................92 N 100 NDisintegration ...............................................2 min < 1 minFriability ..........................................................1% 1%




4. Chemical stability of formulation No. 2 (20–25 °C)


Acetylsalicylic acid 100 % 100 % 100 %Vitamin C 100 % 100 % 96 %Free acetic acid < 0,01% < 0.01%Free salicylic acid < 0,01% < 0.01%


Acetylsalicylic Acid + Vitamin C Tablets (325 mg + 250 mg) page 2


Acetylsalicylic Acid + Vitamin C Tablets(400 mg + 250 mg)

1. Formulation

Acetylsalicylic acid, crystalline (Merck) ......400 gAscorbic acid, powder (BASF) ..................250 gLudipress [1] ...........................................100 gKollidon CL [1] ..........................................20 gMacrogol 6000 powder [6] ...........................3 g




Weight .................................................841 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness ................................................120 NDisintegration ........................................<1 minFriability...................................................0.4 %Free acetic acid ...................................<0.01%Free salicylic acid .....................................0.1%Colour .....................................................white




4. Stability after 12 months (20–25 °C, closed)

Hardness ................................................130 NDisintegration ........................................<1 minFriability...................................................0.8 %Acetylsalicylic acid ..................................100 %Ascorbic acid ..........................................100 %Free acetic acid ...................................<0.01%Free salicylic acid .....................................0.1%Colour of the tablets .................................white


Acetylsalicylic Acid + Vitamin C Tablets (400 mg + 250 mg) page 2


Acetylsalicylic Acid Tablets (400 mg)

1. Formulation

Acetylsalicylic acid, crystalline (Merck) ......400 gLudipress [1] .............................................99 gStearic acid [7] ............................................1 gKollidon CL [1]...........................................15 g


Mix all components, pass through a 0.8 mm sieve and press with low compression force.


Weight .................................................516 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................90 NDisintegration ........................................<1 minFriability...................................................0.4 %Dissolution, 15 min....................................84 %

30 min ...................................97%

4. Chemical stability

Storage time RT 40 °C

0 months 100.0 % 100.0 %6 months 100.0 % 100.0 %

12 months 98.4 % 100.0 %

The content of free salicylic acid remained always below 0.2 %.




Acetylsalicylic Acid Tablets (500 mg)

1. Formulation

Acetylsalicylic acid (Merck) .......................500 gAvicel PH 101 [5] .....................................200 gKollidon 30 [1] ...........................................15 gKollidon CL [1] ..........................................25 gMagnesium stearate [2] ...............................3 g


Pass all components through a 0.8 mm sieve, mix and press with low compression force.


Weight .................................................707 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................61 NDisintegration ........................................<1 minFriability...................................................0.7%




Albendazole Tablets,(100 mg)

1. Formulation

Albendazole ............................................100 gLudipress [1] ...........................................288 gMagnesium stearate [2] ...............................4 gAerosil 200 [4] .............................................8 g




Weight .................................................400 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................99 NDisintegration ..........................................2 minFriability ...................................................0.1%




Alginic Acid + Aluminium Hydroxide + Magnesium Silicate Tablets (500 mg + 100 mg + 25 mg)

1. Formulation

Alginic acid .............................................500 gAluminium hydroxide dried gel (Giulini) ......100 gMagnesium trisilicate .................................25 gSodium bicarbonate.................................170 gSorbitol, crystalline [10] ............................160 gSucrose, crystalline .................................627 gLudipress [1] ...........................................900 gKollidon VA 64 [1] ......................................70 gMagnesium stearate [2]..............................50 gVanillin ........................................................5 g


Pass all components through a 0.8 mm sieve, mix and press with high compression force.


Weight ...................................................2.55 gDiameter ...............................................20 mmForm ...................................................biplanarHardness ................................................120 NFriability...................................................1.3 %




Alpha-Methyldopa Tablet Cores (250 mg), DC

1. Formulation

Alpha-Methyldopa ...................................250 gLudipress [1] ...........................................350 gStearic acid [7] ..........................................15 g




Weight .................................................620 mgDiameter ...............................................11 mmForm ..................................................biconvexHardness ................................................123 NDisintegration ..........................................6 minFriability...................................................0.2 %Dissolution (10 min) ...................................91%

(20 min)...................................98 %

4. Physical stability (20 months, 20–25 ºC)

Weight .................................................620 mgHardness ................................................115 NDisintegration ..........................................7 minFriability...................................................0.5 %Dissolution (10 min) ...................................91%

(20 min) .................................100 %




Alpha-Methyldopa Tablets (500 mg), DC

1. Formulations

No. 1 No. 2

Alpha-Methyldopa .......................................500 g 500 g(Alpha Chemicals)Avicel PH 101 [5] ............................................54 g 200 gKollidon VA 64 [1] ...........................................20 g 30 gKollidon CL [1] ...............................................20 g 20 gTalc [10] .........................................................90 g 8 gAerosil 200 [4]..................................................7 g 1 gMagnesium stearate [2] ....................................2 g –Calcium arachinate [2] .........................................– 1 g


Pass magnesium stearate trough a 0.2 mm sieve and the other compo-nents through a 0.5 mm sieve, mix and press with high compressionforce (Formulation No. 1) and low compression force (Formulation No. 2).


No. 1 No. 2

Weight ..........................................693 mg 750 mgDiameter ...........................................12 mm 12 mmForm ..........................................biplanar biplanarHardness ..............................................80 N 113 NDisintegration ...........................................<1 min 1 – 2 minFriability .............................................0.4 % 0.8 %Dissolution, 4 min ........................................86 % –

16 min ......................................92 % –




4. Remark

In the case of formulation No. 1 it was not possible to press tablet coresof a biconvex form because some capping effect was observed.


Alpha-Methyldopa Tablets (500 mg), DC page 2


Alprazolam Tablets (0.5 mg)

1. Formulation

Alprazolam...............................................0.5 gLudipress [1] ...........................................148 gMagnesium stearate [2] ...............................1 g


Mix all components, sieve through a 0.8 mm screen and press with low compression force.


Weight .................................................158 mgDiameter .................................................8 mmForm ...................................................biplanarHardness ................................................106 NDisintegration ..........................................3 minFriability .................................................<0.1%

4. Remark

If the content uniformity does not meet the requirements it would berecommended to prepare a premix of the active ingredient with a smallpart of the Ludipress or with lactose monohydrate before mixing with theother components of the formulation.




Aluminium Hydroxide + Magnesium SilicateChewable Tablets (120 mg + 250 mg)

1. Formulation

Aluminium hydroxide dried gel (Giulini) ...120.0 gMagnesium trisilicate ............................250.0 gLudipress [1] ........................................232.0 gAerosil 200 [4] ..........................................6.0 gMagnesium stearate [2].............................6.0 gCyclamate sodium ..................................12.0 gMenthol ...................................................1.5 g


Mix all components, pass through a 0.8 mm sieve and press with a compression force of 20 kN.


Weight .................................................640 mgDiameter ...............................................16 mmForm ...................................................biplanarHardness..................................................83 N

4. Remarks

Due to the poor flowability of the powder the tabletting machine shouldbe equipped with a special technical device providing a continuous andhomogenous filling of the dies.




Ambroxol Tablets (30 mg)

1. Formulation

Ambroxol hydrochloride ..........................30.0 gLudipress [1] .........................................217.5 gMagnesium stearate [2].............................2.5 g




Weight .................................................250 mgDiameter .................................................8 mmForm ...................................................biplanarHardness ................................................115 NDisintegration ..........................................7 minFriability...................................................0.2 %Dissolution, 30 min ...................................82 %




Ambroxol HCl Sustained-Release PelletsReleasing Tablets (MUPS-Formulation)

d) Formulation

The formulation is designed for 500g of tablets:

Ambroxol HCl/ Kollicoat® SR 30D pellets* ...250.0gMicrocrystalline cellulose Vivapur® 200 [7] ........................................250.0gMagnesium stearate [8] ..................................2.5g

e) Procedure

Mix the ingredients together, pass through a 0.8mm sieve and compressinto tablets with a force of about 15kN.

Tablet press ................Korsch EK0, 30 tablets/ minCompression force ........................................15kN

f) Tablet properties

Weight .......................................................400mgDiameter .....................................................10mmForm ........................................................biplanarHardness .................................................92-116N

* The pellets are manufactured using the spary suspension described in chapter 4.5.3 underAmbroxol HCI Substained-release pellets (drug-layering process)


2.8 Formulation of tablets obtained by Direct Compression (Lab Scale)



Ambroxol HCl Sustained-Release Pellets Releasing Tablets page 2

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5% Kollicoat SR 30D

10% Kollicoat SR 30D



method: paddle 100 rpm; 37°C0-20h: pH 7.4


Aminophylline Tablets (100 mg), DC

1. Formulations

No. 1 No. 2

Aminophylline powder (BASF)........................100 g 100 gLudipress [1] ................................................150 g –Avicel PH 200 [5].................................................– 200 gKollidon VA 64 [1] ................................................– 6 gMagnesium stearate [2] ....................................2 g 2 gAerosil 200 [4]..................................................2 g 12 g


Mix all components, sieve and press on a rotary press to tablets with lowcompression force.


No. 1 No. 2

Weight ......................................................254 mg 318 mgDiameter ......................................................8 mm 12 mmForm ........................................................biplanar biplanarHardness ......................................................97 N 124 NDisintegration .............................................10 min 1 – 2 minFriability .......................................................0.2 % 0.2 %Dissolution 10 min:........................................87% –

15 min: ......................................100 % –




4. Colour stability of Formulation No. 1

After 2 weeks at room temperature no change of the colour of thetablets was observed but the long term compatibility between amino-phylline and lactose should be controlled.

5. Remark for Formulation No. 2

Due to the reduced flowability the tabletting machine should be equippedwith a special technical device providing a continuous and homogenousfilling of the molds.


Aminophylline Tablets (100 mg) page 2


Amitryptylline Tablets (10 mg and 25 mg)

1. Formulations

No. 1: No. 2:10 mg 25 mg

Amitryptylline...............................................10 mg 25 mgLudipress [1] .............................................139 mg 124 mgMagnesium stearate [2] ....................................1 g 1 mg


Pass all components through a 0.8 mm sieve, mix intensively and presswith low compaction force (8 kN).


No. 1 No. 2

Weight ......................................................152 mg 157 mgDiameter ......................................................8 mm 8 mmForm ........................................................biplanar biplanarHardness ......................................................70 N 92 NDisintegration...........................................1 – 2 min 3 minFriability .......................................................0.3 % 0.2 %




Ampicillin Tablets(250 mg)

1. Formulation

Ampicillin trihydrate .................................250 gLudipress [1] ...........................................250 gMagnesium stearate [2] ..............................10 g




Weight .................................................500 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................84 NDisintegration ..........................................4 minFriability...................................................0.4 %




Asparagus Extract + Parsley Extract Tablets (200 mg + 200 mg)

1. Formulation

Asparagus extract, powder ......................200 gParsley extract, powder ...........................200 gSorbitol, crystalline [10] ............................200 gKollidon VA 64 [1] ......................................20 gKollidon CL [1]...........................................10 gMagnesium stearate [2] ...............................4 g




Weight .................................................636 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................49 NDisintegration ..........................................9 minFriability .....................................................0 %




Aspartame Effervescent Tablets(20 mg)

1. Formulation

Aspartame .............................................20.0 gSorbitol, crystalline [10] ...........................10.4 gTartaric acid, powder ..............................14.3 gSodium bicarbonate................................18.7 gKollidon 25 [1] ..........................................1.7 gPolyethylene glycol 6000, powder [6] .........1.1 g


Mix , pass through a 0.5 mm sieve and press to tablets.


Weight ...................................................66 mgDiameter .................................................6 mmForm ...................................................biplanarHardness..................................................25 NDisintegration ........................................<1 minFriability...................................................0.7%




Aspartame Tablets (25 mg), DC

1. Formulation

Aspartame ................................................27 gLudipress [1] .............................................76 gKollidon CL [1]...........................................12 gMagnesium stearate [2] ...............................1 gLutrol F 68 [1] .............................................3 g


Mix all components, pass through a 0.8 mm sieve and press to tabletswith low compression force.


Weight .................................................120 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................65 NDisintegration ........................................<1 minFriability ...................................................0.1%




Atenolol Tablets (90 mg)

1. Formulation

Atenolol (Stober).....................................93.0 gLudipress [1].........................................287.0 gKollidon CL [1]........................................52.0 gMagnesium stearate [2].............................2.2 gAerosil 200 [4] ..........................................0.9 g




Weight .................................................436 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................85 NDisintegration......................................2 – 3 minFriability .................................................<0.1%




Benzhexol Tablets (5 mg)

1. Formulations

No. 1 No. 2

Benzhexol chloride .......................................5.0 g 5.0 g(= trihexylphenidyl hydrochloride)Ludipress [1]..............................................114.0 g 100.0 gCorn starch [3] ....................................................– 14.5 gMagnesium stearate [2] .................................0.6 g 0.5 gAerosil 200 [4] .....................................................– 1.5 g


Mix all components for 10 minutes in a turbula mixer and press with low compression force.


No. 1 No. 2

Weight ......................................................120 mg 121 mgDiameter ......................................................5 mm 5 mmForm ........................................................biplanar biplanarHardness.....................................................120 N 113 NDisintegration ...............................................7 min 3 minFriability ...................................................< 0.06 % 0.4 %




Berberine Tablets (5 mg)

1. Formulation

Berberine sulfate ......................................5.7 gLactose monohydrate [8].........................54.1 gLudipress [1] ..........................................54.1 gMagnesium stearate [2].............................1.2 g




Weight..................................................115 mgDiameter .................................................6 mmForm ...................................................biplanarHardness..................................................40 NDisintegration ..........................................1 minFriability ...................................................0.1%




Beta Carotene + Vitamin C + Vitamin E Chewable Tablets(3 mg + 50 mg + 25 mg)

1. Formulations

No. 1 No. 2

Betavit® Dry Powder 10 % (BASF....................30 g 30 gAscorbic acid, powder (BASF).........................50 g 50 gDry Vitamin E acetate 50 % DC (BASF) ............50 g 50 gLudipress LCE [1] .........................................365 g –Sorbitol, cryst. [10] ..............................................– 335 gKollidon VA64 [1].................................................– 30 gMagnesium stearate [2] ....................................5 g 5 g


Mix all components, pass through a sieve and press with high compres-sion force.


No. 1 No. 2

Weight ......................................................503 mg 506 mgDiameter ....................................................12 mm 12 mmForm ........................................................biplanar biplanarHardness.....................................................126 N 167 NDisintegration (water)...................................17 min 8 minFriability........................................................0.1% 0.1%




Beta Carotene + Vitamin C + Vitamin E Chewable Tablets(10 mg + 500 mg + 250 mg)

1. Formulation

Beta Carotene dry powder 10 % ...............100 gAscorbic acid, crystalline (BASF) ..............250 gSodium ascorbate, crystalline...................280 gVitamin E acetate dry powder SD 50 ........500 g(BASF)Sorbitol, crystalline [10] ............................600 gLudipress [1] ...........................................500 gFructose .................................................350 gPolyethylene glycol 6000, powder [6]..........50 g


Mix all components, pass through a sieve and press with high compres-sion force.


Weight ..............................................2,600 mgDiameter ...............................................20 mmForm ...................................................biplanarHardness ................................................122 NDisintegration (water) .......................15 – 20 minFriability...................................................0.4 %




Beta Carotene + Vitamin C + Vitamin EEffervescent Tablets(12 mg + 150 mg + 25 mg)

1. Formulation

Lucarotene Dry Powder 10 % CWD G/Y (BASF) .....................................120 gAscorbic acid, crystalline (BASF) ..............150 gDry Vitamin E acetate 50 % DC (BASF) .......50 gLudipress LCE [1] ....................................705 gKollidon VA64 [1] .......................................50 gCitric acid, anhydrous ..............................450 gSodium bicarbonate ................................320 gPolyethylene glycol 6000, powder [10] ........75 gOrange flavour (Dragoco) ...........................50 gAspartame (Searle) ....................................30 g


Mix all components, pass through a sieve and press with high compres-sion force at a maximum of 30 % of relative atmospheric humidity.


Weight ...............................................2045 mgDiameter ...............................................20 mmForm ...................................................biplanarHardness..................................................95 NDisintegration (water) ...............................3 minFriability...................................................0.9 %




Beta Carotene + Vitamin C + Vitamin E Tablets(6 mg + 100 mg + 30 mg)

1. Formulations

No. 1 No. 2

Betavit® dry powder 10 % (BASF) ...................65 g 65 gAscorbic acid, powder (BASF) .......................100 g 100 gVitamin E acetate dry powder 50 % ................60 g 60 gLudipress [1] ................................................369 g –Sorbitol, crystalline (Merck) ..................................– 233 gKollidon VA64 [1].................................................– 30 gKollidon CL [1] ....................................................– 8 gMagnesium stearate [2] ....................................6 g 4 g


Pass all components through a 0.8 mm sieve, mix and press withmedium or high compression force.


No. 1 No. 2

Weight ......................................................599 mg 502 mgDiameter ....................................................12 mm 12 mmForm ........................................................biplanar biplanarHardness ......................................................60 N 59 NDisintegration (water) ....................................7 min 7 minFriability .......................................................0.3 % 0.2 %




4. Chemical stability of beta carotene in Formualtion No. 1(40 °C, closed)

0 weeks 15 weeks

Beta carotene/tablet 8.0 mg 7.8 mg

5. Remarks

A colourant pigment should be added to obtain a homogeneous appea-rance of the tablets.

The tablets of Formulation No. 1 could be commercialized in Europe asdietary food because all components are allowed for this application.


Beta Carotene + Vitamin C + Vitamin E Tablets (6 mg + 100 mg + 30 mg) page 2



1. Formulation

Betavit® dry powder 10 % (BASF) ..............75 gAscorbic acid, powder (BASF)....................60 gVitamin E acetate dry powder 50 % ...........50 gSorbitol, crystalline [10] ............................240 gKollidon CL [1] ..........................................30 gMagnesium stearate [2] ...............................5 g




Weight .................................................497 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................55 NDisintegration ..........................................8 minFriability ................................................< 0.1%

4. Remarks

A colourant pigment should be added to obtain a homogeneous appearance of the tablets.

These tablets could be commercialized in Europe as dietary foodbecause all components are allowed for this application.





1. Formulation

Beta Carotene dry powder 10 % ..............125 gAscorbic acid, crystalline (BASF) ..............125 gSodium ascorbate, crystalline (BASF)........141 gVitamin E acetate dry powder SD 50 .......250 g(BASF)Ludipress [1] or Sorbitol, crystalline [10] ....119 gPolyethylene glycol 6000, powder [10] ..........5 gOrange flavour (FDO) .................................15 gSodium cyclamate .....................................10 g


Mix all components, pass through a sieve and press with medium compression force.


Weight .................................................790 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................50 NDisintegration ...................................not testedFriability ................................................< 0.1%




Beta Carotene Effervescent Tablets(7 mg)

1. Formulation

Lucarotin® dry powder 10 % CWD (BASF) ..70 gLudipress [1]............................................113 gCitric acid, anhydrous ..............................200 gSodium bicarbonate.................................120 gSodium carbonate .....................................12 gSodium cyclamate .....................................20 gAspartame ................................................15 gOrange flavour ..........................................20 gPolyethylene glycol 6000, powder [6]..........30 g


Pass all components through o 0.8 mm sieve, mix and press withmedium or high compression force at maximum 30 % of relative atmos-pheric humidity.


Compression force18 kN 26 kN

Weight ......................................................602 mg 605 mgDiameter ....................................................12 mm 12 mmForm ........................................................biplanar biplanarColour.........................................................brown brownHardness ......................................................81 N 108 NDisintegration (water) ..................................45 sec 50 secFriability .......................................................0.4 % 0.2 %




Beta Carotene Tablets(15 mg)

1. Formulation

No. 1 No. 2

Beta carotene dry powder 10 %..................160.0 g 150.0 gLudipress [1] .............................................240.0 g –Dicalcium phosphate [9], granulated with .............– 175.0 g5 % Kollidon 30Avicel PH 101 [5] .................................................– 100.0 gKollidon CL [1] ..............................................6.0 g 5.0 gAerosil 200 [4] .....................................................– 2.5 gTalc [10] ..............................................................– 20.0 gCalcium arachinate [2] .........................................– 2.5 gMagnesium stearate [2] .................................2.0 g –


Mix all components, pass through a 0.8 mm sieve and press with amedium compression force.


No. 1 No. 2

Weight ......................................................400 mg 502 mgDiameter ....................................................12 mm 12 mmForm ........................................................biplanar biplanarHardness ......................................................59 N 57 NDisintegration .............................................12 min 1 minFriability........................................................0.1% 0 %




4. Chemical and physical stability (20–25 °C)

Formulation No. 1: 6 Months 12 Months

Loss of beta carotene 3 % 4 %Hardness 60 N 59 NDisintegration 9 min 7 minFriability 0.15 % 0.16 %

Formulation No. 2: 6 Months 12 Months

Loss of beta carotene < 8 % 9 %


Beta Carotene Tablets (15 mg) page 2


Bran Tablets (250 mg), DC

1. Formulation

Bran wheat (milled <1 mm).......................250 gLudipress [1] ...........................................200 gKollidon 30 [1] .............................................5 gAerosil 200 [4] .............................................4 gMagnesium stearate [2] ...............................4 g


Mix all components, pass through a sieve and press with medium compression force.



4. Remark

If the bran is not milled, the hardness of tablet is higher but the content uniformity is less.





Bromhexine Tablets(8 mg)

1. FormulationsNo. 1 No. 2

Bromhexine .....................................................8 g 8 gDicalcium phosphate [9]................................179 g –Ludipress [1] .......................................................– 190 gKollidon VA 64 [1].............................................7 g –Kollidon CL [1] .................................................5 g –Magnesium stearate [2] ....................................1 g 1 g


Pass all components through a 0.8 mm sieve, mix and press with low/medium compression force.


No. 1 No. 2

Weight ......................................................204 mg 202 mgDiameter ......................................................8 mm 8 mmForm ........................................................biplanar biplanarHardness ......................................................70 N 70 NDisintegration.............................................< 1 min 1 – 2 minFriability .......................................................0.2 % 0.2 %




Bromocriptine Tablet Cores(6 mg)

1. Formulation

Bromocriptine mesylate ............................6.1 gLudipress [1] ........................................205.5 gMagnesium stearate [2].............................2.2 g


Mix all components, pass through a 0.8 mm sieve and press with high compression force.


Weight .................................................214 mgDiameter .................................................9 mmForm ..................................................biconvexHardness..................................................88 NDisintegration ..........................................4 minFriability...................................................0.7%Dissolution (10 min.) ...............................95.6 %




Calcium Chewable Tablets (200 mg Ca)

1. Formulation

Calcium gluconate (Merck) ....................845.0 gCalcium citrate (Merck) .........................500.0 gLudipress LCE [1] .................................297.5 gCitric acid anhydrous, fine granular ........100.0 g(Jungbunzlauer)Polyethylene glycol 6000, powder [6] .......80.0 gOrange flavour (Dragoco) ........................30.0 gAerosil 200 [4]........................................17.0 g.Aspartame, potassium (Searle) ..................5.0 g




Weight................................................2417 mgDiameter ...............................................20 mmForm ...................................................biplanarHardness................................................201 NFriability...................................................0.2 %




Calcium Glycerophosphate Tablets(200 mg)

1. Formulation

Calcium glycerophosphate ....................200.0 gLudipress [1].........................................297.5 gMagnesium stearate [2].............................2.5 gAerosil 200 [4] ............................................q.s.




Weight .................................................470 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness ................................................131 NDisintegration ..........................................7 minFriability ...................................................0.1%




Captopril Tablet Cores(25 mg)

1. Formulation

Captopril...................................................25 gLudipress [1] .............................................91 gKollidon CL [1] ............................................2 gMagnesium stearate [2] ...............................2 g


Mix all components, pass through a 0.8 mm sieve and press withmedium compression force.


Weight .................................................122 mgDiameter .................................................8 mmHardness..................................................49 NDisintegration ..........................................1 minFriability...................................................0.2 %




Carbamazepine Sustained Release Tablets(200 mg) DC

1. FormulationsA B

Carbamazepine (Fabrica ital. Sintetica) .......200.0 g 200.0 gKollidon SR [1]...........................................100.0 g 100.0 gLudipress LCE [1] ......................................200.0 g 150.0 gKollidon CL-M [1] ................................................– 20.0 gMagnesium stearate [2] .................................2.5 g 2.5 g


All ingredients were passed through a 0.8 mm sieve, blended for 10 minin a Turbula mixer and the compressed with high compression force.


A B

Weight ...................................................502.5 mg 472.5 mgDiameter ....................................................12 mm 12 mmHardness.....................................................140 N 164 NFriability ......................................................0.14 % 0.06 %




4. Dissolution of Carbamazepine


Carbamazepine Sustained Release Tablets (200 mg) DT page 2

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Carbamazepine Tablets(200 mg)

1. Formulation

Carbamazepine .......................................200 gLudipress [1] ...........................................300 gMagnesium stearate [2] ...............................2 g




Weight .................................................496 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness ................................................128 NDisintegration ..........................................1 minFriability...................................................0.3 %Dissolution 10 min:....................................75 %

30 min: ...................................83 %60 min: ...................................86 %




Carbonyl Iron + Copper Sulfate + Manganese Sulfate Tablets (24 mg + 0.16 mg + 3.5 mg)

1. Formulation

Carbonyl iron OF (BASF) .........................24.0 gCopper sulfate........................................0.16 gManganese sulfate ...................................3.5 gLudipress [1] ........................................100.0 gMagnesium stearate [2].............................2.0 g




Weight .................................................131 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................95 NDisintegration......................................2 – 3 minFriability...................................................0.3 %




Cetylpyridinium Lozenges (2.5 mg)

1. Formulation

Cetylpyridinium chloride (Merck) ................2.5 gLudipress LCE [1] .................................370.0 gPolyethylene glycol 6000, powder [6] .......20.0 gMenthol, crystalline...................................6.0 gAspartame, potassium (Searle) ..................1.5 g


Mix all components, pass through a 0.8 mm sieve and press with lowcompression force.


Weight .................................................402 mgDiameter ...............................................10 mmForm ...................................................biplanarHardness..................................................80 NDisintegration.......................................>10 minFriability ................................................< 0.1%




Chlorhexidine Lozenges (5 mg)

1. Formulation

Chlorhexidine (Sigma) ...............................5.0 gSorbitol, crystalline [10] .........................150.0 gKollidon VA64 [1] ......................................5.0 gMenthol, crystalline...................................5.0 gEucalyptol, crystalline ...............................5.0 gAspartame, potassium..............................1.0 gSaccharin, sodium....................................0.1 gAerosil 200 [4] ..........................................2.0 gMagnesium stearate [2].............................1.0 g




Weight .................................................175 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................63 NDisintegration.......................................>10 minFriability...................................................0.3 %




Choline Theophyllinate Tablets(100 mg)

1. Formulation

Choline theophyllinate ..............................100 gLudipress [1] ...........................................244 gMagnesium stearate [2] ...............................6 g


Pass all components through a 0.5 mm sieve mix and press with verylow compression force.


Weight .................................................350 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................70 NDisintegration ..........................................4 minFriability ................................................< 0.1%




Chymotrypsine Tablets(27 mg)

1. Formulation

Chymotrypsine .......................................27.5 gLudipress [1] ..........................................71.5 gMagnesium stearate [2].............................1.0 g


Mix all components, pass through a 0.8 mm screen and press with low compression force.


Weight .................................................100 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................67 NDisintegration ..........................................6 minFriability ................................................< 0.1%




Cimetidine Effervescent Tablets(400 mg)

1. Formulations

No. 1 No. 2

Cimetidine ...................................................400 g 400 gLudipress LCE [1] .........................................680 g 400 gSodium bicarbonate .....................................600 g 500 gTartaric Acid.................................................450 g –Citric Acid...........................................................– 400 gAspartame (Searle) .........................................30 g 27 gPolyethylene glycol 6000, powder [6] ..............90 g 75 gOrange flavour (Dragoco) .................................q.s. q.s.


Pass the mixture through a 0.8 mm screen and press with medium com-pression force at a maximum of 30 % of relative atmospheric humidity.


No. 1 No. 2

Weight ....................................................2250 mg 1780 mgDiameter ....................................................20 mm 16 mmForm ........................................................biplanar biplanarHardness.....................................................107 N 195 NDisintegration (water) ....................................4 min < 2 minFriability .......................................................1.0 % 1.0 %




Cimetidine Tablets(200 mg)

1. Formulation

Cimetidine...............................................200 gLudipress [1] ...........................................295 gMagnesium stearate [2] ...............................5 g


Pass the mixture through a 0.8 mm screen and press with low compres-sion force.


Weight .................................................510 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................92 NDisintegration ..........................................1 minFriability...................................................0.2 %Dissolution (15 min) ...................................88 %




Clenbuterol Tablets(20 µg)

1. Formulation

Clenbuterol hydrochloride .......................0.02 gLudipress [1] ........................................99.00 gMagnesium stearate [2]...........................1.00 g


Mix all components in a turbula mixer and press to tablets with a compression force of 20 kN.


Weight .................................................100 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................75 NDisintegration ..........................................3 min

4. Remark

If the content uniformity does not meet the requirements it would be recommended to prepare a premix of clenbuterol hydrochloride with asmall part of the Ludipress before mixing with the other components ofthe tabletting mixture.




Clobazam Tablets(10 mg)

1. Formulation

Clobazam...............................................10.0 gDicalcium phosphate, DI-TAB [9] ...........135.0 gKollidon VA 64 [1] .....................................7.0 gKollidon CL [1] ..........................................7.0 gMagnesium stearate [2].............................1.5 g


Mix all components, pass through a 0.8 mm sieve and press withmedium compression force (15 kN).


Weight .................................................165 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................44 NDisintegration ........................................< 1 minFriability ................................................< 0.1%




Clomifen Citrate Tablets(50 mg)

1. Formulation

Clomifen citrate ......................................50 mgLudipress [1].........................................100 mgMagnesium stearate [2].............................1 mg


Mix all components, sieve and press with low compression force.


Weight .................................................154 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................82 NDisintegration ..........................................6 minFriability .................................................0.13 %Dissolution (60 min) .................................100 %




Cyproheptadine Tablet(4 mg)

1. Formulation

Cyproheptadine ..........................................4 gLudipress [1] ...........................................194 gMagnesium stearate [2] ...............................2 g


Pass all ingredients through a 0.8 mm sieve. Mix and press with very low compression force (4 kN).


Weight .................................................202 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................46 NDisintegration ......................................... 3 minFriability...................................................0.5 %

4. Remark





Diazepam Tablet(10 mg)

1. Formulation

Diazepam..................................................10 gLudipress ......................................100 – 480 gMagnesium stearate .........................0.5 – 2.0 g


Mix all components, pass through a 0.8 mm sieve and press withmediumcompactation force.


Weight .........................................110 – 490 mg.............................according to the formulationForm ...................................................biplanarHardness .............................................> 100 NDisintegration ........................................< 5 minFriability ................................................< 0.1%Dissolution (10 min) .................................100 %




Diclofenac Na-dispers-tablet (50 mg)

a) Formulation

Diclofenac Na .......................................50.0mgAvicel® PH 102 .................................143.8mgKollidon® CL........................................50.0mgAerosil® 200 ..........................................5.0mgMagnesium stearate ...............................1.0mg

b) Procedure

Mix the ingredients together, pass through a 0.8mm sieve and compressinto tablets with a force of about 10kN.

Tablet press ...................Korsch PH106, 30 rpmCompression force ................................11.8kN

c) Tablet properties

Weight ...............................................248.0mgS rel ........................................................1.7%Diameter ................................................10mmForm ...................................................biplanarHardness...................................................93NFriability ................................................< 0.1%




d) Dissolution

e) Content


Diclofenac Na-dispers-tablet (50 mg) page 2

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Diclofenac Sustained ReleaseTablets(100 mg)

1. Formulation

Diclofenac sodium (Ivotec).....................100.0 gKollidon SR [1]......................................100.0 gSilicon dioxide, colloidal [4] .......................3.4 gMagnesium stearate [2].............................3.4 g


All ingredients were passed through a 0.8 mm sieve, blended for 10 minin a Turbula mixer and then compressed with medium compression force.


Weight ..............................................206.4 mgDiameter .................................................8 mmHardness ................................................195 NFriability.................................................0.09 %

4. Dissolution of Diclofenac-sodium



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Diclofenac Tablets(50 mg)

1. Formulation

Diclofenac sodium ..................................50.0 gLudipress [1] ........................................150.0 gMagnesium stearate [2].............................1.5 gPolyethylene glycol 6000, powder [6] .......15.0 gKollidon CL [1] ........................................10.0 g




Weight .................................................226 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................72 NDisintegration ........................................16 minFriability .................................................<0.1%Dissolution (10 min) ...................................58 %

(15 min) ...................................77%(30 min)...................................99 %




Diltiazem Tablets(50 mg)

1. Formulation

Diltiazem...................................................60 gLudipress [1] ...........................................141 gPolyethylene glycol 6000, powder [6]............5 gAerosil 200 [4] .............................................1 gMagnesium stearate [2] ...............................1 g




Weight .................................................215 mgDiameter .................................................8 mmForm ...................................................biplanarHardness .............................................> 100 NDisintegration .........................................6 minFriability ...................................................0.1%




Dimenhydrinate Tablets(50 mg), DC

1. Formulation

Dimenhydrinate .........................................50 gAerosil 200 [4] ..........................................4.0 gLudipress [1] ...........................................140 gKollidon CL [1] .........................................2.0 gMagnesium stearate [2].............................1.5 g


Mix dimenhydrinate with Aerosil 200, add the other components, sieveand press with low compression force.


Weight .................................................202 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................76 NDisintegration .........................................3 minFriability .................................................<0.1%Dissolution in water (USP, 15 min ...............91%

30 min ...............93 %45 min ...............94 %




Doxazosin Mesylate Tablets(1 mg and 4 mg)

1. Formulations

1 mg 4 mg

Doxazosin mesylate .........................................1 g 4 gLudipress [1] ..................................................98 g 95 gMagnesium stearate [2] ....................................1 g 1 g


Mix all components, sieve and press with low compression force.


1 mg 4 mg

Weight ......................................................100 mg 102 mgDiameter ......................................................6 mm 6 mmForm ........................................................biplanar biplanarHardness ......................................................65 N 66 NDisintegration ...............................................3 min 3 minFriability .....................................................< 0.1% < 0.1%Dissolution in water (USP), 5 min ..................85 % 67%

10 min.................100 % 100 %




Enteric Film Coating of Tablets (Organic Solution)

(Acetylsalicylic Acid 100mg)

a) Formulation of the cores

Component Company mg/Tablet

ASA Synopharm 100.0Ludipress BASF 148.5Avicel PH 102 FMC 50.0Magnesium stearate Bärlocher 1.5Total 300.0

b) Manufacture by direct compression:

All the components were mixed for 10 minutes, passed through a sieveof a size of 0.8 mm and compressed into tablets on a rotary press with arate of 40.000 tablets/h at a compression force of 15 kN. Core shapewas convex with a diameter of 9mm and the engraving “BASF”.

Hardness of the tablets was about 60 N.

c) Formulations of the coating suspension:

The formulation is for 5 kg of cores (diameter 9 mm; 300 mg)

Component Parts by weight [g]

No.1 No.2

Kollicoat MAE 100 P 344.52 344.52Triethyl citrate 34.45 34.45Ethanol 4214.60 -Isopropanol/Wasser (70/30) – 4214.60 Total 4593.57 4593.57

Polymer applied: 10.0 mg/cm2

Content of polymer: 7.5 %




c) Preparation of the spray suspension

Kollicoat MAE 100P and triethyl citrate were stirred into the solvent untilcomplete dissolution.

d) Process Parameters:

Coating pan:............................24” Accela CotaSize of batch: ............................................5 kgInlet air temperature: ...............................50 °COutlet air temperature:........................35-38 °CProduct temperature: .........................30-35 °CInlet air rate: ...........................................70 m_Outlet air rate:.......................................140 m_Spraying pressure: ................................2.0 barNozzle diameter:...................................1.0 mmRate of spraying: ................................30 g/minTime of spraying:......................................2.5 hPre heating ..............................................3 minFinal drying:.............................................5 min

f) Dissolution:

• the drug release is carried out according to USP monograph AspirinDelayed-Release Tablets


Enteric Film Coating of Tablets (Organic Solution) (Acetylsalicylic Acid 100 mg) page 2

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method: paddle 100rpm; 37°C0-2h: 0.08 M HCL2 h +: phosphate buffer pH 6.8


Ethambutol Tablets(400 mg), DC

1. Formulation

Ethambutol .............................................400 gSorbitol, crystalline [10] ............................200 gKollidon VA 64 [1] ......................................20 gKollidon CL [1]...........................................10 gMagnesium stearate [2] ..............................10 g


Mix all components, pass through a 0.8 mm sieve and press withmedium/high compression force.


Weight .................................................620 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................82 NDisintegration.........................................10 minFriability...................................................0.8 %




Etophylline + Theophylline Tablets(100 mg + 22 mg), DC

1. Formulation

Etophylline, powder .................................101 gTheophylline, anhydrous 0,2/0,7 (BASF) .....23 gLudipress [1] .............................................53 gMagnesium stearate [2] ...............................1 gAerosil 200 [4] .............................................2 g




Weight .................................................175 mgDiameter .................................................8 mmForm ...................................................biplanarHardness ................................................102 NDisintegration......................................7 – 8 minFriability...................................................0.2 %

4. Remark

To enhance the flowability of the tabletting mixture the amount of Aerosil200 could be increased.




Famotidine Tablets(40 mg)

1. Formulations

No. 1 No. 2

Famotidine.....................................................40 g 40 gLudipress [1] ................................................105 g 104 gMagnesium stearate [2] ....................................3 g –Stearic acid [7] ....................................................– 2 gAerosil 200 [4]..................................................4 g 4 g




No. 1 No. 2

Weight ......................................................149 mg 148 mgDiameter ......................................................8 mm 8 mmForm ........................................................biplanar biplanarHardness ......................................................74 N 49 NDisintegration (gastric juice)...........................3 min 1 minFriability......................................................<0.1% 0.3 %Dissolution (10 min)........................................63 % not tested

(30 min) .......................................95 % not tested




Ferrous Fumarate Tablets(200 mg)

1. Formulation

Ferrous fumarate .....................................200 gLudipress [1] ...........................................295 gMagnesium stearate [2] ...............................5 g








Ferrous Sulfate + Manganese Sulfate + Copper Sulfate Tablets(65 mg + 3.5 mg + 0.16 mg)

1. Formulation

Ferrous sulfate, anhydrous ......................65.0 gManganese sulfate ...................................3.5 gCopper sulfate........................................0.16 gLudipress [1] ..........................................70.0 gKollidon 30 [1] ........................................10.0 gMagnesium stearate [2].............................2.0 gAerosil 200 [4] ..........................................3.0 g




Weight .................................................149 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................28 NDisintegration .....................................3 – 4 minFriability...................................................0.4 %




Ferrous Sulfate Tablets(200 mg)

1. Formulation

Ferrous sulfate, anhydrous .......................203 gLudipress [1] ...........................................185 gKollidon VA 64 [1] ......................................15 gMagnesium stearate [2] ...............................4 gTalc [10] ......................................................4 gAerosil 200 [4] .............................................3 g


Mix all components, pass through a 0.8 mm sieve and press to tabletswith medium compression force.


Weight .................................................413 mgDiameter .................................................8 mmForm ...................................................biplanarHardness ................................................110 NDisintegration.........................................13 minFriability...................................................0.2 %




Fluoxetine Tablets (20 mg)

1. Formulation

Fluoxetine HCl (BASF).............................22.4 gLudipress [1].........................................176.0 gMagnesium stearate [2].............................1.6 g




Weight .................................................205 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................76 NDisintegration ..........................................5 minFriability ...................................................0.1%




Folic Acid Tablets (5 mg)

1. Formulation

Folic acid .................................................5.0 gLudipress [1] ........................................195.0 gMagnesium stearate [2].............................1.5 g




Weight .................................................213 mgDiameter .................................................8 mmForm ...................................................biplanarHardness................................................205 NDisintegration ..........................................7 minFriability ................................................< 0.1%

4. Remark





Furosemide Tablets(40 mg)

1. Formulation

Furosemide ...............................................40 gLudipress [1] ...........................................158 gMagnesium stearate [2] ...............................2 g








Furosemide Tablets(200 mg)

1. Formulation

Furosemide .............................................200 gLudipress [1] ...........................................388 gMagnesium stearate [2] ...............................6 gAerosil 200 [4] .............................................6 g




Weight .................................................618 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness ................................................159 NDisintegration .....................................3 – 4 minFriability...................................................0.2 %




Garlic Extract + Thyme Extract TabletsCores with Vitamin C(300 mg + 25 mg + 100 mg)

1. Formulation

Garlic extract, granulated (Aflopa).............300 gThyme extract, powder (Aflopa) ..................25 gAscorbic acid, crystalline (BASF)...............100 gKollidon CL [1]...........................................14 gLudipress [1] ...........................................268 gMagnesium stearate [2] ...............................7 g




Weight..................................................714 mgDiameter ...............................................12 mmForm ..................................................biconvexHardness..................................................50 NDisintegration ..........................................9 minFriability .....................................................0 %




Ginkgo Extract Tablets(40 mg)

1. Formulation

Ginkgo biloba extract, dry powder ............240 g(Biogen)Aerosil 200 [4] .............................................1 gKollidon CL [1] ............................................4 gLudipress [1] ...........................................203 gMagnesium stearate [2] ...............................2 g


Mix the Ginkgo extract with Aerosil 200, add the other components,pass through a 0.8 mm sieve and press to tablets with low compressionforce.


Weight ......................................................254 mgDiameter ......................................................8 mmForm ........................................................biplanarHardness ......................................................81 NDisintegration ...............................................8 minFriability .....................................................< 0.1%




Glibenclamide (Glyburide) Tablets(5 mg)

1. Formulation

No. 1 No. 2

Glibenclamide micronized (Guidotti)................5.0 g –Glibenclamide .....................................................– 5.0 gLudipress [1] .............................................120.0 g 194.0 gMagnesium stearate [2] .................................0.5 g 1.0 g


Mix all components, pass through a 0.8 mm sieve and press with low compression force (about 10 kN).


No. 1 No. 2

Weight ......................................................125 mg 201 mgDiameter ......................................................7 mm 8 mmForm ........................................................biplanar biplanarHardness ......................................................80 N 107 NDisintegration ............................................2-3 min 3 – 4 minFriability .....................................................< 0.2 % < 0.1%Dissolution (pH 7.4) (10 min) ...........................50 % –

(30 min) ...........................69 % –(60 min) ...........................75 % –




4. Influence of the compression force on the physical tablet properties(Formulation No. 2)

Compression forceProperty 5 kN 10 kN 20 kN 25 kN

Hardness 47 N 107 N 158 N 191 NDisintegration 2 – 3 min 3 – 4 min 3 – 4 min 5 minFriability < 0.1% < 0.1% < 0.1% < 0.1%


Glibenclamide (Glyburide) Tablets (5 mg) page 2


Griseofulvin Tablets(125 mg)

1. Formulation

Griseofulvin, micronized (Aldrich) ..............125 gLudipress [1] ...........................................250 gPolyethylene glycol 6000, powder [6] ..........10 gAerosil 200 [4] ...........................................19 g


Pass all components through a 0.5 mm sieve, mix and press with low compression force applying a vibrating hopper.


Weight .................................................367 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................79 NDisintegration ..........................................1 minFriability...................................................0.3 %Dissolution, 20 min ...................................78 %

40 min ...................................88 %60 min ...................................92 %

4. Remark

The flowability of the tabletting mixture should be increased by higheramounts of Ludipress or/and Aerosil 200.




Hydrochlorothiazide + Potassium ChlorideTablet Cores (50 mg + 300 mg)

1. Formulation

Hydrochlorothiazide...................................50 gPotassium chloride ..................................300 gKollidon CL [1]...........................................15 gAerosil 200 [4] .............................................2 gMagnesium stearate [2] ...............................2 g


Pass all components through a 0.8 mm sieve, mix and press.


Weight .................................................369 mgDiameter .................................................9 mmForm ..................................................biconvexHardness..................................................88 NDisintegration ........................................< 1 minDissolution of hydrochlorothiazide, .............89 %10 min




Hydrochlorothiazide Tablets(50 mg), DC

1. Formulation

Hydrochlorothiazide...................................50 gLudipress [1] ...........................................280 gMagnesium stearate [2] ...............................2 g








Ibuprofen Tablets(400 mg), DC

1. Formulations

Ibuprofen (Francis) ...................................400 gAerosil 200 [4] ............................................ 4 gLudipress [1] ...........................................342 gKollidon CL [1] ............................................8 gMagnesium stearate [2] ...............................8 g


Pass ibuprofen and magnesium stearate through a 200 µm sieve, mixwith the other components and press with medium compression force.


Weight ......................................................752 mgDiameter ....................................................16 mmHardness .....................................................112 NDisintegration ..........................................2 – 3 minFriability .......................................................0.4 %Dissolution, 10 min ........................................82 %

15 min.........................................91%

4. Physical stability (20–25ºC)


Hardness – 121 N 120 NDisintegration – 2 – 3 min –Friability – 0.4 % 0.2 %Dissolution, 10 min 85 % – 89 %

20 min 87% 91% 88 %




Ibuprofen Tablets (600 mg), DC

1. Formulations

Ibuprofen 50 (BASF) ................................600 gAerosil 200 [4] .............................................9 gAvicel PH 200 [5] .....................................108 gKollidon VA 64 [1] ......................................50 gKollidon CL [1] ..........................................27 gMacrogol 6000 powder [6] ...........................6 g


Mix ibuprofen with Aerosil 200, add the other components and presswith low compression force.


Weight .................................................793 mgDiameter ...............................................16 mmHardness..................................................80 NDisintegration ........................................<1 minFriability...................................................0.8 %




4. Dissolution (Storage 20-25°C)


Ibuprofen Tablets (600 mg), DC page 2

100

80

60

40

20

00 3

Months

6 9

10 min

15 min

30 min

drug

rele

ased

[%]

12


Indomethacin Sustained Release Tablets(75 mg)

1. Formulation

Indomethacin (Synopharm) ........................75 gKollidon SR [1].........................................125 gLudipress LCE [1] ....................................100 gSilicon dioxide, colloidal [4] .......................1.5 gMagnesium stearate [2].............................1.5 g


All ingredients were passed through a 0.8 mm sieve, blended for 10 minin a Turbula mixer and then compressed with medium compression force.


Diameter ...............................................10 mmWeight .................................................303 mgHardness ................................................163 NFriability .................................................0.01%

4. Dissolution of Indomethacin



100

80

60

40

0

20

0 128 18104 62 1614time [h]

75 rpm medium:phosphate buffer pH 6.2

rele

ased

dru

g [%

]


Indomethacin Tablets(50 mg), DC

1. Formulation

Indomethacin ............................................50 gLudipress [1] ...........................................227 gKollidon CL [1] ..........................................20 gMagnesium stearate [2] ...............................3 g




Weight .................................................303 mgDiameter .................................................8 mmForm ...................................................biplanarHardness ................................................176 NDisintegration ..........................................3 minFriability...................................................0.2 %




Indomethacin Tablets(100 mg)

1. Formulation

Indomethacin ..........................................100 gLudipress [1] ...........................................397 gMagnesium stearate [2] ...............................3 g





4. Remark

If the flowability of indomethacin is not good it should be mixed with alow percentage of Aerosil 200.




Isosorbide Dinitrate Tablets(5 mg)

1. Formulation

Isosorbide dinitrate + Lactose (4+6) .........12.5 gLactose monohydrate [8] .......................152.1 gKollidon 30 [1] ..........................................5.4 gKollidon CL [1] .........................................9.0 gMagnesium stearate [2].............................1.0 g




Weight .................................................184 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................45 NDisintegration .......................................< 1 minFriability ...................................................0.1%




Khellin Tablets(25 mg)

1. Formulation

Khellin ......................................................25 gLudipress [1] ...........................................124 gMagnesium stearate [2] ...............................1 g


Pass all components through a 0.8 mm sieve, mix intensively and presswith low compression force (10 kN).


Weight .................................................150 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................65 NDisintegration .................................about 1 minFriability.................................................0.25 %




Labetalol Tablets(50 mg)

1. Formulation

Labetalol, fine powder (Joy Sun)..............50.0 gLudipress [1] ..........................................98.4 gAerosil 200 [4] ..........................................0.8 gMagnesium stearate [2].............................0.8 g


Mix all components, sieve through a 0.8 mm screen and press with low compression force.


Weight .................................................150 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................71 NDisintegration ..........................................1 minFriability...................................................0.2 %Dissolution (gastric juice,paddle, 50 rpm) 10 min............96.6 %

15 min .............100 %




Levamisole Tablets(150 mg)

1. Formulation

Levamisole hydrochloride .........................150 gLudipress [1] ...........................................300 gMagnesium stearate [2] ...............................4 g




Weight .................................................458 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................80 NDisintegration .....................................3 – 4 minFriability...................................................0.2 %




Levothyroxine Tablets (0.05 mg)

1. Formulations

No. 1 No. 2

I. Levothyroxine sodium..................................0.05 g 0.05 gCitric acid, anhydrous..........................................– 10.00 gMagnesium stearate ....................................1.00 g 1.00 g

II. Ludipress [1] .............................................99.00 g 89.00 g


Prepare premix I, add II and pass the mixture thorugh a 0.8 mm sieve.Mix and press with low compression force.


No. 1 No. 2

Weight ......................................................103 mg 101 mgDiameter ......................................................6 mm 6 mmForm ........................................................biplanar biplanarHardness ......................................................52 N 45 NDisintegration...........................................1 – 2 min 4 minFriability........................................................0.1% <0.1%Content uniformity not controlled

4. Remarks

If the content uniformity of formulation No. 1 does not meet the require-ments it would be recommended to add a small part of Ludipress (= part II) to the premix I.

The function of citric acid in formulation No. 2 is the stabilization of the active ingredient. The effectiveness was not controlled in this formulation.




Lisinopril Tablets(10 mg)

1. Formulation

Lisinopril ...................................................10 gLudipress [1] ...........................................139 gMagnesium stearate [2] ...............................1 g


Pass all components through a 0.8 mm sieve, mix intensively and presswith low compactation force (10 kN).






Lycopene Tablet Cores(6 mg)

1. Formulation

LycoVit 10 % dry powder............................60 gLudipress [1] ...........................................330 gKollidon CL [1] ............................................6 gMagnesium stearate [2] ...............................4 g


Mix the LycoVit dry powder with the other components, sieve through a0.8 mm screen and press with medium to high compression force.


Weight .................................................400 mgDiameter ...............................................11 mmForm ..................................................biconvexHardness..................................................80 NDisintegration ..........................................4 minFriability .................................................<0.1%






Magaldrate Chewable Tablets(500 mg)

1. Formulation

I. Magaldrate USP ......................................500 gLactose monohydrate [8] .........................400 gOrange flavour (FDO) .................................50 g

II. Kollidon 90 F [1] ........................................20 gBanana flavour (FDO)...................................6 gCocos flavour (FDO) ....................................6 gSaccharin sodium........................................1 gWater ......................................................180 g

III. Aerosil 200 [4] .............................................5 gMagnesium stearate [2] ...............................3 g

2. Manufacturing (Wet granulation)

Granulate mixture I with solution II, pass through a 0.8 mm sieve, dry,mix with III and press with low compression force.


Weight................................................1000 mgDiameter ...............................................16 mmForm ...................................................biplanarHardness..................................................72 NDisintegration (water) .............................60 minFriability ................................................< 0.1%Taste .......................................................good


Magaldrate Chewable Tablets (1000 mg)

1. Formulation

Magaldrate (Reheis) ...............................1000 gLudipress LCE [1] ....................................930 gLutrol E4000F [1] .......................................60 gAspartame, potassium (Searle) ...................10 gPeppermint flavour .....................................q.s.




Weight ..............................................2,000 mgDiameter ...............................................20 mmForm ...................................................biplanarHardness..............................................>250 NFriability .................................................<0.1%




Magaldrate Dispersible Tablets(700 mg)

1. Formulation

Magaldrate..............................................700 gLactose monohydrate [8] .........................435 gKollidon 90 F [1] ........................................10 gKollidon CL [1] ..........................................50 gMagnesium stearate [2] ...............................5 g


Pass all components through a 0.8 mm sieve, mix and press with low compression force (4 – 6 kN).


Weight ..............................................1,200 mgDiameter ...............................................16 mmForm ...................................................biplanarHardness ................................................125 NDisintegration (water)..............................25 secFriability ...................................................0.1%




Magnesium Carbonate Tablets(260 mg)

1. Formulation

Magnesium carbonate USP......................262 gLudipress [1] ...........................................238 gMagnesium stearate [2] ...............................4 g




Weight .................................................499 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness ................................................168 NDisintegration ..........................................1 minFriability ................................................< 0.1%




Mebendazole Tablets (100 mg)

1. Formulation

Mebendazole...........................................100 gLudipress [1] ...........................................196 gMagnesium stearate [2] ...............................4 g








Meprobamate + Phenobarbital Tablets(400 mg + 30 mg), DC

1. Formulation

Meprobamate..........................................400 gPhenobarbital............................................30 gAvicel PH 101 [5] .......................................76 gKollidon VA 64 [1] ......................................13 gKollidon CL [1] ..........................................21 gTalc [10] ......................................................8 gAerosil 200 [4] .............................................1 gCalcium arachinate [2] .................................1 g




Weight .................................................551 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................87 NDisintegration ........................................< 1 minFriability...................................................0.9 %




Meprobamate Tablets(400 mg), DC

1. Formulation

Meprobamate..........................................400 gAvicel PH 101 [5] .......................................80 gCorn starch [3] ..........................................30 gKollidon VA 64 [1] ......................................20 gKollidon CL [1] ..........................................20 gTalc [10] ......................................................7 gMagnesium stearate [2] ...............................3 g


Mix all components, pass through a 0.8 mm sieve and press with high compression force (20 KN).


Weight .................................................560 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................90 NDisintegration ......................................< 10 minFriability ..................................................0.6 %




Metamizol Tablets(500 mg)

1. Formulations

No. 1 No. 2

Metamizol sodium ........................................500 g 500 g(= Dipyrone)Ludipress [1] ................................................100 g –Avicel PH 101 [5] .................................................– 100 gKollidon 30 [1].....................................................– 15 gKollidon CL [1] ...............................................10 g 25 gMagnesium stearate [2]...................................10 g –Aerosil 200 [4]..................................................5 g 1 gTalc [10] ..............................................................– 8 gCalcium arachinate [2] .........................................– 1 g




No. 1 No. 2

Weight ......................................................625 mg 654 mgDiameter ....................................................12 mm 12 mmForm ........................................................biplanar biplanarHardness.....................................................120 N 62 NDisintegration ...............................................5 min 2 minFriability .......................................................0.3 % 1%




Methyl Cysteine Tablets(100 mg)

1. Formulation

Methyl cysteine hydrochloride ..................100 gLudipress [1] ...........................................200 gMagnesium stearate [2].............................3 mgMenthol ...................................................4 mg






Weight .................................................307 mgHardness..................................................85 NDisintegration......................................2 – 3 minFriability...................................................0.2 %




Metoclopramide Tablets(10 mg)

1. Formulation

Metoclopramide hydrochloride ................10.0 gLudipress [1] ..........................................89.5 gMagnesium stearate [2].............................0.5 g




Weight .................................................100 mgDiameter .................................................6 mmForm ...................................................biplanarHardness..................................................35 NDisintegration (gastric juice) ......................3 minFriability ...................................................0.1%Dissolution (15 min) .................................100 %


Weight .................................................100 mgHardness..................................................35 NDisintegration (gastric juice) ......................3 minFriability ...................................................0.1%Dissolution (15 min) .................................100 %




Metronidazole Tablet Cores(400 mg)

1. Formulation

Metronidazole .........................................400 gAvicel PH 102 [5] .....................................150 gKollidon VA 64 [1] ......................................25 gKollidon CL [1]...........................................15 gAerosil 200 [4] .............................................5 gPolyethylene glycol 6000, powder [6]..........50 g


Mix all components, pass through a 0.8 mm sieve and press with high compression force (25 – 30 kN).


Weight .................................................645 mgDiameter ...............................................12 mmForm ..................................................biconvexHardness..................................................87 NDisintegration......................................1 – 2 minFriability ................................................< 0.1%




Metronidazole Tablets(200 mg)

1. Formulation

Metronidazole .........................................200 gAvicel PH 101 [5] .....................................200 gKollidon 30 [1] .............................................6 gKollidon CL [1]...........................................10 gAerosil 200 [4] .............................................5 gMagnesium stearate [2] ...............................5 g


Mix all components, pass through a 0.8 mm sieve and press with high compression force (25 – 30 kN).


Weight .................................................426 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness ................................................133 NDisintegration......................................1 – 2 minFriability ................................................< 0.1%




Multivitamin + Calcium + Iron Tablets(1 RDA of Vitamins)

1. Formulation

Vitamin A acetate dry powder ...................5.0 g500,000 i. u./g (BASF)Vitamin D dry powder ..............................2.0 g100,000 i. u./g (BASF)Thiamine mononitrate (BASF) ....................1.2 gRiboflavin (BASF)......................................1.8 gNicotinamide ..........................................12.0 gVitamin E acetate dry powder SD 50 ........4.0 g(BASF)Ascorbic acid, powder (BASF) .................50.0 gFerrous fumarate ....................................60.0 gDibasic calcium phosphate [9], .............200.0 ggranulated with 5 % Kollidon 30 [1]Calcium carbonate................................125.0 gAvicel PH 101 [5] ....................................45.0 gAerosil 200 [4] ..........................................1.5 g


Mix all components, pass through a sieve and press to tablets.


Weight .................................................500 mgDiameter ...............................................11 mmForm ...................................................biplanarHardness..................................................75 NDisintegration (water)...........................2 – 3 minFriability...................................................0.3 %




Multivitamin + Carbonyl Iron Tablets(1–2 RDA of Vitamins)

1. Formulation

Vitamin A acetate dry powder500,000 i. u./g (BASF) .............................10.0 gThiamine mononitrate (BASF) ....................2.2 gRiboflavin (BASF)......................................2.2 gNicotinamide ..........................................16.5 gCalcium D-pantothenate (BASF) ..............11.5 gPyridoxine hydrochloride (BASF)................2.2 gCyanocobalamin, dry powder 0.1% ..........6.0 gAscorbic acid, powder (BASF) .................85.0 gVitamin E acetate dry powder SD 50 .......31.0 g(BASF).............................................................Ludipress [1].........................................311.0 gCarbonyl iron powder OF (BASF) .............10.0 gMagnesium stearate [2].............................3.0 gOrange flavour..........................................7.2 gSaccharin sodium.....................................2.5 g


Mix all ingredients, pass through a 0.8 mm sieve, mix and press withhigh compression force (20 kN).


Weight .................................................500 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness..................................................69 NDisintegration.........................................12 minFriability...................................................0.2 %




Multivitamin + Minerals Tablets with BetaCarotene(1 RDA of Vitamins)

1. Formulation

Beta carotene dry powder, Betavit 20% ........16.5 g(BASF)Thiamine mononitrate (BASF) .........................1.7 gRiboflavin (BASF)...........................................1.9 gNicotinamide (Degussa) ...............................22.0 gCalcium D-pantothenate (BASF) ...................12.0 gPyridoxine hydrochloride (BASF) ....................2.2 gAscorbic acid, cryst. (BASF).........................72.0 gVitamin E acetate dry powder 50 % (BASF) ...66.0 gFerrous fumarate .........................................54.7 gMagnesium oxide, high density type ..........165.8 g(Merck)Copper II oxide, powder (Merck) ....................2.5 gManganese sulfate (Merck) ............................6.9 gZink oxide (Merck) .......................................18.7 gPotassium chloride (Baker) ..........................76.3 gDicalium phosphate, DI-TAB [9] ..................550.0 gAvicel PH 102 [5] .........................................60.0 gCroscarmellose [5] ......................................32.0 gSyloid® 244 FP (Grace) ..................................6.0 gStearic acid [7] ..............................................6.0 gMagnesium stearate [2] .................................6.0 g


All ingredients were passed through a 0.8 mm sieve, blended in a Tur-bula mixer and then compressed with medium to high compressionforce.


Weight ................................................1193 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness ................................................112 NFriability ...................................................0.1%




4. Stability of beta carotene

Because beta carotene may be the most sensitive vitamin in this formu-lation it’s stability at room temperature and at 40°C/75 % relative humi-dity was determined


Multivitamin + Minerals Tablets with Beta Carotene (2 RDA of Vitamins) page 2

50

60

70

80

90

100

20-25°C40°C/75% r.h.

20 40 600Weeks

Bet

a ca

rote

ne c

onte

nt, %


Multivitamin + Minerals Tablets with BetaCarotene(2 RDA of Vitamins)

1. Formulation

No. 1 No. 2

Beta carotene dry powder 10 %..................150.0 g 50.0 gThiamine mononitrate (BASF) .........................2.5 g 3.0 gRiboflavin (BASF)...........................................2.9 g 3.0 gPyridoxine hydrochloride (BASF) ....................2.0 g 3.0 gNicotinamide...............................................22.0 g 22.0 gCalcium D-pantothenate (BASF) ...................12.0 g 12.0 gAscorbic acid for direct compression ..........110.0 g 100.0 g(Roche)Calcium phosphate, dibasic [9] ..................550.0 g 550.0 gFerrous fumarate .........................................82.0 g 80.0 gMagnesium oxide ......................................166.0 g 160.0 gCupric sulfate................................................2.5 g 2.0 gManganese sulfate ......................................13.8 g 14.0 gPotassium chloride ......................................57.2 g 50.0 gZinc sulfate .................................................37.0 g 37.0 gAvicel PH 102 [5] .........................................57.0 g 60.0 gKollidon CL [1] ............................................50.0 g 50.0 gStearic acid [7] ..............................................5.7 g 6.0 gMagnesium stearate [2] .................................5.0 g 5.0 g


Mix all components, pass through a 0.8 mm sieve and press with high compression force.





No. 1 No. 2

Weight ....................................................1300 mg 1205 mgDiameter ....................................................16 mm 16 mmForm ........................................................biplanar biplanarHardness ......................................................94 N 88 NDisintegration (water) ..................................< 1 min < 1 minFriability ..........................................................1% < 0.1%

4. Chemical stability of formulation No. 2 (20–25°C)

Storage time Beta Carotene B1 B2 B5 B6 C

6 Months 100 % 98 % 98 % 100 % 97% 95 %12 Months 92 % 96 % 92 % 99 % 96 % 94 %

5. Remark



Multivitamin + Minerals Tablets with Beta Carotene (2 RDA of Vitamins) page 2


Multivitamin Chewable Tablets for Children

1. Formulation

Vitamin A acetate dry powder....................7.0 g500,000 i. u./g (BASF)Thiamine mononitrate (BASF) ....................1.2 gRiboflavin (BASF)......................................1.2 gNicotinamide ..........................................20.0 gPyridoxine hydrochloride (BASF)................1.8 gCyanocobalamin 0.1% dry powder ............6.5 g(BASF)Ascorbic acid, powder (BASF) .................60.0 gVitamin D3 acetate dry powder100,000 i. u./g (BASF) ...............................5.0 gVitamin E acetate ..................................31.0 gdry powder SD 50 (BASF)Sorbitol, crystalline [10] .........................200.0 gSucrose, crystalline...............................200.0 gKollidon VA 64 [1] ...................................20.0 gAerosil 200 [4] ..........................................1.0 gOrange flavour, dry powder .....................30.0 gRaspberry flavour, dry powder...................6.0 gPassion fruit flavour, dry powder................3.0 gCyclamate sodium....................................2.0 g


Mix all ingredients, pass through a 0.8 mm sieve and press with mediumto high compression force (20 kN).





Weight .................................................575 mgDiameter ...............................................12 mmForm ...................................................biplanarHardness ................................................100 NDisintegration ..........................................7 minFriability...................................................0.2 %


Multivitamin Chewable Tablets for Children page 2


Multivitamin Effervescent Tablets I, DC(1 – 2 RDA of Vitamins)

1. Formulation

Lucarotene Dry Powder 10 % .................23.0 gCWD G/Y (BASF)Dry Vitamin E acetate 50 % DC (BASF).....40.0 gThiamine mononitrate (BASF) ....................2.0 gRiboflavin C (BASF) ..................................2.0 gNicotinamide ..........................................22.0 gCalcium D-pantothenate (BASF) ..............11.0 gPyridoxine hydrochloride (BASF)................2.0 gCyanocobalamin 0.1% dry powder ............6.0 gAscorbic acid, powder (BASF) .................85.0 gLudipress LCE [1] .................................477.0 gSodium bicarbonate .............................600.0 gTartaric acid .........................................400.0 gPolyethylene glycol 6000, powder [6] ......90.0 gOrange flavour (Dragoco) ........................60.0 gApartame (Searle) ...................................30.0 g


Mix all components, pass through a 0.8 mm sieve, mix and press withhigh compression force at a maximum of 30 % of relative atmospherichumidity.


Weight................................................1850 mgDiameter ...............................................20 mmForm ...................................................biplanarHardness..................................................91 NDisintegration (water) ...............................1 minFriability ..................................................0.6 %




Multivitamin Effervescent Tablets II, DC(3–4 RDA of Vitamins)

1. Formulations

No. 1 No. 2

Thiamine mononitrate (BASF) .........................5.5 g 5.5 gRiboflavin (BASF)...........................................5.5 g 5.5 gPyridoxine hydrochloride (BASF) ...................6.5 g 6.5 gNicotinamide ............................................60.0 g 60.0 gCalcium D-pantothenate (BASF)...................30.0 g 30.0 gAscorbic acid, powder (BASF) ....................200.0 g 200.0 gCyanocobalamin 0.1% dry powder ...............20.0 g 20.0 gVitamin A palmitatedry powder 325000 i. u./g CWD (BASF) ........30.0 g 30.0 gVitamin E acetate dry powder 50 % .............110.0 g 50.0 gCitric acid, powder ..............................................– 500.0 gTartaric acid, powder .................................400.0 g –Sodium bicarbonate ..................................500.0 g 500.0 gLudipress [1] ..........................................600.0 g 500.0 gPolyethylene glycol 6000, powder [6]............70.0 g 70.0 gSaccharin sodium .........................................0.5 g 0.5 gCyclamate sodium.......................................40.0 g 40.0 gSucrose, crystalline ...................................200.0 g 200.0 gFructose ..........................................200.0 g 200.0 gFlavours (Firmenich) ...................................100.0 g 100.0 g


Mix all components, sieve through a 0.8 mm screen and press with high compression force at maximum 30 % relative atmospheric humidity.





No. 1 No. 2

Weight ....................................................2200 mg 2495mgDiameter ....................................................20 mm 20 mmForm ........................................................biplanar biplanarHardness ......................................................98 N 197 NDisintegration (water)................................1 – 2 min 2 minFriability .......................................................1.0 % 0.4 %

4. Chemical stability of formulation No. 1 (after 12 months at 20–25 ºC;HPLC)

Vitamin B1 ...................................................93 %Vitamin B6 ...................................................89 %Vitamin B12...................................................88 %Vitamin A ......................................................79 %All other vitamins .........................................> 95 %


Multivitamin Effervescent Tablets II, DC (3–4 RDA of Vitamins) page 2


Multivitamin Tablet Cores with Beta-Carotene(1–2 RDA of Vitamins)

1. Formulation

Vitamin mixture (BASF, see “Remark”)....270.2 gLudipress [1] ..........................................69.1 gMagnesium stearate [2].............................3.3 g




Weight .................................................459 mgDiameter ...............................................11 mmForm ..................................................biconvexHardness..................................................97 NDisintegration (water)..............................13 minFriability .....................................................0 %Content uniformity of Vitamin B1,B2, B6 and folic acid ................conform to DAB




4. Remark

The used vitamin mixture had the following composition:

Vitamin A acetate dry powder .....................1.27%500,000 i. u./gBeta carotene dry powder BetaVit 10 %......11.50 %Thiamine mononitrate..................................1.24 %Riboflavin ..................................................0.96 %Nicotinamide.............................................11.50 %Calcium D-pantothenate .............................1.91%Pyridoxine hydrochloride .............................1.15 %Cyanocobalamin gelatin coated 1% .............2.86 %D-Biotin, 1% trituration ...............................1.91%Folic acid ...................................................0.09 %Ascorbic acid............................................38.20 %Vitamin D3 dry powder 100,000 i. u./g..........0.76 %Vitamin E acetate dry powder 50 DC..........28.40 %Phytomenadione dry powder 5 % GFP..........0.19 %


Multivitamin Tablet Cores with Beta-Carotene (1–2 RDA of Vitamins) page 2


Multivitamin Tablets, DC(1–2 RDA of Vitamins)

1. Formulation

No. 1 No. 2

Vitamin A acetate dry powder ......................10.0 g 10.0 g500,000 i. u./g (BASF) ...........................................Thiamine mononitrate (BASF) .........................2.2 g 2.2 gRibolfavin (BASF)...........................................2.2 g 2.2 gNicotinamide ...............................................16.5 g 16.5 gCalcium D-pantothenate (BASF) ...................11.5 g 11.5 gPyridoxine hydrochloride (BASF) ....................2.2 g 2.2 gCyanocobalamin 0.1% dry powder.................6.0 g 6.0 gAscorbic acid, powder (BASF)......................85.0 g 85.0 gVitamin E acetate dry powder SD 50 ...........31.0 g 31.0 g(BASF)Ludipress [1] .............................................321.0 g –Microcrystalline cellulose, Vitacel®.......................– 300.0 g(Rettenmaier)Kollidon VA 64 [1] ................................................– 21.0 gMagnesium stearate [2] .................................3.0 g 3.0 gOrange flavour ..............................................7.2 g 7.2 gSaccharin sodium .........................................2.5 g 2.5 g


Mix all components, pass through a 0.8 mm sieve, mix and press withmedium compression force (15 kN).





No. 1 No. 2

Weight ......................................................500 mg 501 mgDiameter ....................................................12 mm 12 mmForm ........................................................biplanar biplanarHardness ......................................................68 N 195 NDisintegration (water) ....................................5 min 6 minFriability .......................................................0.2 % < 0.1%

4. Chemical stability of formulation No. 1 (after 12 months at 20–25 ºC)

Vitamin A ..............................................88 %Vitamin B6 ..............................................94 %Calcium D-pantothenate ................................92 %Vitamin B12 ..................................................... 90 %All other vitamins .........................................> 95 %


Multivitamin Tablets, DC (1–2 RDA of Vitamins) page 2


Multivitamin Tablets for Dogs

1. Formulation

Vitamin A + D3 dry powder ......................4.0 g500,000 + 50,000 i. u./g (BASF)Thiamine mononitrate (BASF) ....................0.5 gRiboflavin (BASF)......................................0.7 gNicotinamide ............................................5.0 gCalcium D-pantothenate (BASF)................1.0 gPyridoxine hydrochloride (BASF)................0.5 gCyanocobalamin gelatin coated 1% ..........0.5 g(BASF)Folic acid ...............................................0.05 gCholine bitartrate ....................................20.0 gVitamin E acetate dry powder SD 50 ......20.0 g(BASF)Ludipress [1] ........................................196.0 gMagnesium stearate [2].............................2.0 g




Weight .................................................250 mgDiameter .................................................8 mmForm ...................................................biplanarHardness..................................................77 NDisintegration (water) ...............................7 minFriability .....................................................0 %




Multivitamin Tablets with Beta Carotene(1–2 RDA of Vitamins)

1. Formulations

No. 1 No. 2

Beta Carotene dry powder 10 % Betavit® .....10.0 g –(BASF) .................................................................Beta Carotene dry powder 10 % ..........................– 70.0 gPharma (BASF)Thiamine mononitrate (BASF) .........................2.0 g 2.2 gRiboflavin (BASF)...........................................2.0 g 2.2 gNicotinamide ...............................................16.0 g 6.5 gCalcium D-pantothenate (BASF) ...................11.0 g 11.5 gPyridoxine hydrochloride (BASF) ....................2.0 g 2.2 gCyanocobalamin 0.1% dry powder.................6.0 g 6.0 gAscorbic acid, powder (BASF)......................85.0 g 85.0 gVitamin E acetate dry powder SD 50 ............31.0 g 32.0 g(BASF)Ludipress [1] .............................................321.0 g 210.0 gKollidon VA 64 [1] ................................................– 7.0 gMagnesium stearate [2] .................................3.0 g 3.0 gOrange flavour ..............................................7.0 g 7.0 gSaccharin sodium .........................................2.0 g 2.5 g


Mix all components, pass through a 0.8 mm sieve, mix and press withmedium compression force.





No. 1 No. 2

Weight ..........................................508 mg 449 mgDiameter ...........................................12 mm 12 mmForm ..........................................biplanar biplanarHardness ..............................................72 N 47 NDisintegration (water) ....................................5 min 10 minFriability ...........................................< 0.1% 0.15 %

4. Chemical stability of vitamins in formulation No. 1 (20–25 °C, HPLC)

Storage time Beta Carotene B1 B2 B5 B6 C

6 Months 100 % 100 % 90 % 100 % 98 % 96 %12 Months 100 % 98 % 87% 100 % 97% 94 %

5. Remark

Formulation No. 1 could be commercialized in Europe as dietary foodbecause all components are allowed for this application.


Multivitamin Tablets with Beta Carotene (1–2 RDA of Vitamins) page 2


Multivitamin Tablets with Copper and Zinc

1. Formulation

Vitamin mixture (BASF, see “Remark”) .....1000 gAerosil 200 [4] .............................................5 gLudipress [1] ...........................................150 gAvicel PH102 [5] ......................................120 gKollidon VA64 [1] .......................................25 gMagnesium stearate [2] ..............................10 gTalc [10] ....................................................10 g




Weight ...............................................1350 mgDiameter ...............................................16 mmForm ...................................................biplanarHardness..................................................62 NDisintegration (water) ...............................3 minFriability...................................................1.0 %




4. Remark

The used vitamin mixture had the following composition:Thiamine mononitrate...............................3.9 %Riboflavin 100 ..........................................0.4 %Nicotinamide ..........................................10.1%Calcium D-pantothenate ..........................2.9 %Pyridoxine hydrochloride ..........................1.2 %Cyanocobalamin gelatin coated 0.1% .......2.6 %Folic acid .................................................0.1%Ascorbic acid fine powder ......................63.4 %Vitamin E acetate dry powder 500 SD .......9.1%Cupper oxide...........................................0.3 %Zinc sulphate ...........................................6.0 %


Multivitamin Tablets with Copper and Zinc page 2


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