formulation and evaluation of orodispersible tablets of amlodipine besilateijprsonline004

Int. J. Pharm. Res. Sci., 2013, 01(1), 26-32. ISSN: 2348 –0882

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FORMULATION AND EVALUATION OF ORODISPERSIBLE TABLETSOF AMLODIPINE BESILATE.

Udgirkar D.B, Bhalsing M.D*, Rao K.S, Gawali V.B.RRKS College of Pharmacy,Bidar,Karnatka, India

======================================================ABSTRACT:

In the present study an attempt was made toformulate Orodispersible tablets ofamlodipine besilate with a view to provide aconvenient mean of administration to thosepatients suffering from isolated systolichypertension and Angina. Orodispersibletablets of Amlodipine Besilate usingdifferent superdisintegrants were preparedby direct compression method. TheSuperdisintegrants used in this study wereCroscarmellose sodium (CCS),Crospovidone (CP) and Sodium StarchGlycolate (SSG) in varying concentrations(4%, 6% & 8%). The prepared tablets wereevaluated for post compressional parameterssuch as hardness, friability, thickness, in-vitro dispersion time, wetting time, andwater absorption ratio. Effect ofsuperdisintegrants [such as croscarmellosesodium, sodium starch glycolate,crospovidone] on wetting time, in-vitrodispersion time and stability parameter hasbeen studied. In-vitro dispersion time

Corresponding Author: Bhalsing MDRRKS College of Pharmacy,Bidar,Karnatka,IndiaEmail: [email protected]: 17.11.2013Revised: 09.12.2013Accepted: 16.12.2013

decreases with increase in the concentrationof croscarmellose sodium and in-vitrodispersion time increases with increase inconcentration of sodium starch glycolate.However in-vitro dispersion time value didnot reflect major change with increase in theconcentration of crospovidone. The tabletsprepared by direct compression methodcontaining 8 % of croscarmellose sodiumshowed highest in vitro drug release of98.23 % within 30 min. From this study it isconcluded that Orodispersible tablets couldbe prepared by direct compression methodusing different superdisintegrants enhanceddissolution will lead to improvedbioavailability, improved effectiveness ofAmlodipine besilate.

Keywords: Orodispersible tablets,Amlodipine Besilate, Croscarmellosesodium, Crospovidone and Sodium StarchGlycolate

INTRODUCTION:Amlodipine Besilate, is 3-Ethyl 5-

methyl 2- (2-aminomethoxymethyl) -4- (2-chlorophenyl)-1,4-dihydro-6methylpyridine-3, 5-dicarboxylate monobenzene sulphonate.Calcium channel blocker used in treatment


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of hypertension and angina (chronic, stableor vasopastic).1,2

Solid dosage forms like tablet andcapsule are most popular and preferred drugdelivery system because they have highpatient compliance, relatively easy toproduce, easy to market, accurate dosing,and good physical and chemical stability.3

However, many patient groups such as theelderly, children, and patients who arementally retarded, uncooperative, nauseated,or on reduced liquid-intake/ diets havedifficulties swallowing these dosage forms.Those who are traveling or have little accessto water are similarly affected.4 For thesereasons, tablets which can rapidly dissolveor disintegrate in the oral cavity haveattracted a great deal of attention. Rapidlydissolving or disintegrating tablets are notonly indicated for people who haveswallowing difficulties, but also are ideal foractive people.5

Many patient find difficulties toswallow tablet and hard gelatin capsule,consequently they do not take medication asprescribed. It is estimated that 50% of thepopulation is affected by this problem

which result high incident of incomplianceand ineffective therapy.6 This disorder isalso associated with number of medicalconditions including stroke, Parkinson’sdisease, AIDS, head and neck radiationtherapy and other neurological disordersincluding cerebral palsy. Recent advances innovel drug delivery system aim to enhancesafety and efficacy of drug molecule byformulating a convenient dosage form forbetter patient compliance.7

The growing importance of mouthdissolving tablet was underlined recentlywhen European Pharmacopoeia adopted theterm “Orodispersible Tablet” as a tablet thatto be placed in the mouth where it dispersesrapidly before swallowing. Suitable drugcandidates for such systems includeneuroleptics, cardiovascular agents,analgesics, antiallergics and drugs forerectile dysfunction.8 To overcome thisweakness, scientist have developedinnovative drug delivery system known asfast dissolving “melt in mouth” or mouthdissolve (MD) tablet. These are novel typeof tablet that disintegrate dissolve / dispersein saliva.9

MATERIAL & METHODS:Amlodipine besilate was obtained as

a gift sample from Emcure pharma. Ltd.,Pune. croscarmellose sodium (CCS) &crospovidone (CP) obtained as a gift samplefrom cipla , sodium starch glycolate (SSG)& aspartame procured from Himedia labs,mumbai. Directly compressiblemicrocrystalline cellulose (MCC) andmannitol (directly compressible) wereprocured from SD fine chem. Other reagentswere of analytical grade.Method:Preparation of orodispersible tablets ofAmlodipine besilate by directcompression method:

Orodispersible tablets of Amlodipinebesilate were prepared by directcompression. All the ingredients werepassed through 60-mesh separately. Thenthe ingredients were weighed and mixed ingeometrical order and compressed intotablets of 150mg using 8mm round flatpunches on multi station rotary punch tabletcompression machine. (Clit Pilot pressChamnnda Gujarat) A batch of 30 tablets ofeach formulation was prepared for all thedesigned formulations. Differentformulations compositions are given in(Table 1).


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Ingredients (mg)

Formulation code

F1 F2 F3 F4 F5 F6 F7 F8 F9

Amlodipine besilate 10 10 10 10 10 10 10 10 10

MCC 80 80 80 80 80 80 80 80 80

Mannitol 41.3 38.3 35.3 41.3 38.3 35.3 41.3 38.3 35.3

CCS 6 9 12 - - - - - -

SSG - - - 6 9 12 - - -

CP - - - - - - 6 9 12

Aspartame 10 10 10 10 10 10 10 10 10

Mixed fruit flavor 1 1 1 1 1 1 1 1 1

Talc 1 1 1 1 1 1 1 1 1

Magnesium Sterate 0.70 0.70 0.70 0.70 0.70 0.70 0.70 0.70 0.70

Total weight 150 150 150 150 150 150 150 150 150

FormulationCode

Averageweight*

Hardness*(kg/cm2)

Friability(%)

WettingTime*(sec)

Waterabsorption ratio*

InvitroDisintegrationTime* (sec)

DrugContent (%)

F1149 1.78 3.6 0.11 0.81 67 2.51 70 1.54 32 2.78 98.05

F2 148 1.32 3.7 0.11 0.64 65 2.0 72 1.86 31 1.0 96.11

F3 150 0.56 3.9 0.10 0.31 61 2.40 78 1.35 28 1.0 99.44

F4 149 1.97 3.7 0.12 0.62 76 1.89 56 1.58 48 2.0 96.94

F5 150 0.65 3.8 0.18 0.47 73 2.20 63 1.21 50 1.5 97.50

F6 150 1.93 3.6 0.10 0.65 69 1.0 68 1.57 53 1.7 96.66

F7 149 1.21 3.7 0.15 0.82 69 2.25 63 1.20 38 2.8 99.16

F8 149 1.50 3.6 0.21 0.80 67 2.15 68 1.05 35 1.45 98.88

Table 1: Formulation of Amlodipine besilate orodispersible tablets prepared by directcompression method

Table 2: Evaluation of tablets


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%DrugRelease

%DrugRelease

%DrugRelease

F9 151 0.18 3.9 0.10 0.64 65 1.0 71 1.73 34 1.28 97.22

* Average of three determinations.

120100806040200

F1

F2

F3

0 10 20 30 40

Time in min.

Fig 1: Release profile of Amlodipine besilate tablets containing croscarmellose sodium

120

100

80

60

40

20

0

0

F4

F5

F6

10 20 30 40

Time in min.

Fig 2: Release profile of Amlodipine besilate tablets containing sodium starch glycolate.

120

100

80

60

40

20

0

0 5

F7

F8

F9

10 15 20 25 30 35

Time in min.


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Fig 3: Release profile of Amlodipine besilate tablets containing crospovidone.

Wb is weight of tablet after waterabsorption.The results are shown in Table 2.5. In-vitro disintegration time:12 One tableteach was placed in each of the six tubes

Evaluation of Amlodipine besilateOrodispersible tablets:1. Average Weight :10 Twenty tablets wereselected at a random and average weightwas calculated. Then individual tablets wereweighed and the individual weight wascompared with an average weight.2. Hardness and Friability:10 Tablets wereevaluated for hardness and friability testusing Monsanto hardness tester and Rochefriabilator respectively. The percentagefriability was then calculated by,

Winitial - WfinalF = x100Winitial

3. Content uniformity test:11 Four tabletsweighted and crushed in a mortar thenweighed powder contain equivalent to 10mg of drug was taken and dissolved in 100ml methanol, from this solution 1 ml ofsolution was diluted to 10 ml methanolagain 1 ml solution from this diluted upto 10ml with methanol and assayed for drugcontent at 237.5 nm4. Wetting Time and water absorptionratio:10 Wetting time and water absorptionratio is intimately related to thehydrophilicity of the excipient and to thepore size of tablets. A piece of tissue paperfolded twice was placed in a small Petri‐dish(internal diameter of 6.5 cm) containing 10ml of water. A tablet was placed on thepaper and the time required for completewetting was measured. The wetted tabletwas then weighed. Water absorption ratio‘R’ was determined using the equation,R=100{(Wa‐Wa)/Wa}Where, Wa is weight of tablet before waterabsorption,

basket. Add a disc to each tube and run theapparatus using pH 7.4 maintained at37±2C as the immersion liquid. Theassembly should be raised and loweredbetween 30 cycles per minute in the pH 7.4maintained at 37±2C. The time in secondstaken for complete disintegration of thetablet with no palpable mass remaining inthe apparatus was measured and recorded.6. Dissolution Studies:13 Dissolution ratewas studied by using USP type-II apparatus(USP XXIII Dissolution Test Apparatus at50 rpm) using 900ml of phosphate buffer pH(7.4) as dissolution medium. Temperature ofthe dissolution medium was maintained at370.5°C, aliquot of dissolution mediumwas withdrawn at every 5 min interval andfiltered. The absorbance of filtered solutionwas measured by UV spectrophotometricmethod at 237.5 nm and concentration of thedrug was determined from standardcalibration curve.

RESULTS AND DISCUSSIONIn this study total nine formulation of

amlodipine orodispersible tablets wereformulated direct compression techniqueusing croscarmllose sodium, Crospovidoneand Sodium starch glycolate assuperdisntegrants. The post‐compressionparameters such as hardness, friability,weight variation, amount of drug content;in‐vitro wetting time and in‐vitrodisintegration time were evaluated which areshown in table 2.1. Average Weight: The weight variation ofall the tablets tested was within thepharmacopoeial limits. The weights oftablets of various batches were between 148-151 mg.


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2. Hardness and Friability: It is wellknown that the hardness of the tablet canmarkedly affect the release rate of drug. Thehardness was found to be in the range of3.10 to 3.90 kg/cm2. It indicates goodmechanical strength with a capability toresist physical and perfunctory stressconditions during handling.The friabilityvalues of all the formulations are less than1% and they meet the pharmacopoeialstandards3. Content uniformity test:. Thepercentages drug contents of all the tabletswere found to be between 96.11 to 99.44which was within the acceptable limits asmentioned for normal amlodipine tabletsmentioned in USP4. Wetting Time and water absorptionratio: The results of in‐vitro wetting timeand water absorption ratio were found to bewithin the prescribe limits and satisfy thecriteria of orodispersible tablets. Wettingtime for all formulation batches prepared bydirect compression method showed widevariation in the range of 61 and 76 seconds.This wide variation range was observed dueto developmental changes in formulation.

Wetting time for all theseformulation batches varied in the followingincreasing order: Croscarmellose sodium <Crospovidone < Sodium starch glycolate.

The formulations prepared by directcompression technique shows waterabsorption ratio in the range 56 to 78 %formulations containing only 4% ofsuperdisintegrant shows lower waterabsorption ratio when compared toformulations 8% of superdisintegrant, thewater absorption ratio also decreases due toless swelling property. It was observed thatas concentrations of CCS increases waterabsorption ratio increases due to CCS ismade by cross- linking reaction of sodiumCMC. This cross linking greatly reducedwater solubility of sodium CMC while

permitting material to swell and absorbswater many times of its weight.5. Invitro disintegration time: Theformulation showed ideal characteristic of adispersible type tablet. The rate ofdisintegration of formulations increased withvariation in concentration of variousdisintegrants. Batch F3, containing a higheramount of croscarmellose sodium,disintegrates rapidly than other batches andshowed increased disintegration time.6. Dissolution Studies: The invitrodissolution profile indicate the faster andmaximum of 97.56 % drug release within 30min from formulation F3 proving thedisintegrating property of Croscarmellosesodium. It was observed that whenpreparation containing Croscarmellosesodium comes in contact with water, it getsexaggerated immediately causing a quickrupture there by releasing the entire drugwithin the small time lap. The utmost raisein the dissolution rate with varioussuperdisintegrants was found to beCroscarmellose sodium> Crospovidone >SSG shown in fig1, 2, 3.

CONCLUSIONIn the present study the disintegratingproperties of the croscarmellose sodium,Crospovidone and Sodium starch glycolatehad been studied. All the disintegrantsshowed a rapidly disintegration, which isrequired for faster drug dissolution andimproved bioavailability. Croscarmellosesodium has the lead over others, thusproving its future prospects as asuperdisntegrants in orodispersible tabletsfor rapid absorption, effective therapy andpatient compliance. The batch F3 containingcroscarmellose sodium 8% was found to bethe best as compare to other formulations asthis formulation has optimum hardness (3.9kg/cm2), friability (0.31), wetting time (61sec.) and disintegration time of (28 sec). Byan appropriate combination of excipients it


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was thus possible to obtain orallydisintegrating tablets of Amlodipine besilateusing simple and conventional techniques.REFERENCES:

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formulation and evaluation of orodispersible tablets of amlodipine besilateijprsonline004

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