Introduction of Tablets & Evaluation parameters

Submitted to Submitted byD.r Sonali Singh Pooja Joshi M.pharm I

Sem

Pharmacology

CONTENTS Definition General properties. Advantages Disadvantages Classification of tablets Tablet Design and formulation Evaluation tests for compressed and coated

tablets

Defination Tablet is defined as a compressed solid dosage form

containing medicaments with or without excipients.

According to Indian Pharmacopoeia pharmaceutical tablets are solid, flat, or biconvex dishes, unit dosage form , prepared by compressing a drugs or a mixture of drugs, with or without excipients.

They vary in shape and differ greatly in size and weight, depending on amount of medicinal substances and the intended mode of administration.

It is the most popular dosage form and 70% of the total medicines are dispensed in the form of tablet.

General Properties Accurate dosage of medicament , uniform in

weight, appearance and diameter.

Have the strength to withstand the rigors of mechanical shocks encountered in its production, packaging, shipping and dispensing.

Release the medicinal agents in the body in a predictable and a reproducible manner.

Elegant product, acceptable size and shape.

Chemical and physical stabilities.

Advantages Production aspects Large scale production at lowest cost. Easiest and cheapest to package and ship. Greatest chemical and microbial stability over all

dosage form.

User aspects (doctor, pharmacist, patient)

Easy to handling. Lightest and more compact. Greatest dose precision & least content variability. Coating can mask unpleasant tastes & improve

patient acceptability.

Disadvantages Some drugs resist compression into compacts.

Drugs with poor wetting, slow dissolution, intermediate to large dosages may be difficult or impossible to formulate and manufacture as a tablet that provide adequate or full drug bioavailability.

Bitter taste drugs, drugs with an objectionable odor, or sensitive to oxygen or moisture may require encapsulation or entrapment prior to compression or the tablets may require coating.

Classification of tablet

Use wise

structure wise

Action wise

• Tablet for oral ingestion• In oral cavity• By other routes• To prepare solution

• Divisible tablet• Aperture tablet• Concave-convex tablet• Core tablet• Layered tablet

• Modified release tablet• Delayed action tablet e.g :- enteric coated Bisacodyl tablet

Oral tablet for ingestion Standard compressed tablet e.g.; Paracetamol

tablet Multiple compressed tablet I. Compression tablet * Sugar coated tablet * Film coated tablet * Gelatin coated tablet * Enteric coated tablet II. Layered tablet III. Inlay tablet Targeted tablet * Floating tablet * Colon targeting tablet Chewable tablet Dispersible tablet

Tablets used in the oral cavity Lozenges and troches Sublingual tablet e.g. vitamin-c tablet Buccal tablet e.g. vitamin-c tablet Dental cones Mouth dissolved tablet/ rapidly dissolving

tabletTablets administered by other routes

Vaginal tablet e.g. clotrimazole tablet Rectal tablet Hypodermic tablet Implants

Tablets used to prepare solution Effervescent tablet e.g, Disprin tablet

(Asprin) Molded tablets * Hypodermic tablets * Dispensing/ solution tablet e.g, enzyme

tablet (Digiplex) Tablet triturates e.g, Enzyme tablet (Digiplex)

Standard compression tablet

These are the standard uncoated tablets made by either

• direct compression• wet granulation• dry granulation They may be used for local action in GIT/

systemic action In addition to medicinal agents they usually

contain a number of pharmaceutical adjuvants

Multiple compression tablet I. Compression coated tablet Function like sugar-coated or film-coated

tablets or gelatin-coated, enteric coated. Coating of a tablet may• mask a bitter taste, odor, color of the

substance• conceal an unpleasant or mottled

appearance• provide physical and chemical protection

from gastric juice• control the release of drug from the tablet

* film coated tablet * sugar coated tablet

Layered tablet Multilayer tablets (2-3) are prepared by

repeated compression of powders and are made primarily to separate incompatible drugs from each other.

It makes possible to produce repeat-action or prolonged-action products.

for e.g. Admixture containing Phenylephedrine HCL and ascorbic acid with Paracetamol.

Paracetamol + phenylephedrine HCL——› one layer

Paracetamol + ascorbic acid ——› another layer

Targeted tablets Under this category we have two

types of tablets: I. Gastro-retentive tablet Opted when API release is desired in

stomach (antacids, API’s used against H.pylori infection.

• Floating tablet to retain the drug for longer time

period in stomach following approaches can be used:

low density tablet tablet that can expand in gastric

environment(swelling or unfolding). Using muco-adhesive polymer. Drugs like diazepam, levodopa and

ciprofloxacin are sucessfully marketed.

II. Colonic tablets

For the drugs having poor absorption in stomach or small intestine, colonic drugs delivery is an answer of choice.

The pH of this region varies from 6.4 to 7 and presence of microbial flora plays an important role in drug release.

Various mechanism adopted for drug release in this area are: Coating with Ph sensitive polymer e.g. Eudragit S100 and L 100 Biodegradable polymer which are sensitive to colonic bacteria.

Bio-adhesive polymer e.g. poly carbophils/polyethanes.

Redox sensitive polymers.

Chewable tablets Chewable tablets are to be chewed and

thus mechanically disintegrated in the mouth, so that NO DISINTEGRANT IS ADDED.

Flavoring, sweetening and coloring agents are important.

Sorbitol and mannitol are common examples of fillers in chewable tablets.

Provide quick and complete disintegration of the tablet and thus obtain a rapid drug effect after swallowing and dissolution.

Easy administration, especially for infants and elderly people.

Examples: Chewable asprin tablet Antacid tablet

Dispersible Tablets Disintegrate either rapidly in water to form

stabilized suspension or disperse instantaneously in the mouth to be swallowed without the aid of water.

The properties such as porosity, hardness, DT, increase in viscosity after dispersion are necessary to investigate during manufacturing.

ADVANTAGES For pediatric patients who cannot swallow. For API’s unstable if formulated in liquid

formulation. Faster onset of action compared to standard

compressed tablet.Example:- Analgesics( Asprin, Ibuprofen, etc..)

Lonzenges and trouches Lonzenges are flavored medicated dosage

forms intended to be sucked and held in mouth or pharynx.

Two lonzenges forms include hard (or boiled) candy lonzenges and compressed tablet lonzenges (Trouches)

Lonzenges may be used for: Local medications in the mouth and throat, e.g. local anesthetics, anti-

histamines, decongestion, analgesics, demulcents, antiseptics & antibiotics.

Systemic drug uptake No disintegrant is included in compressed

lonzenges composition. Common binder used:- gelatin, common

fillers are (sorbitol, mannitol, and glucose)

Sublingual tablets Reguirements of sublingual tablets

are speed of absorption and a correspondingly rapid physiological response.

Intended to be placed beneath the tongue and held there until absorption has taken place.

Absorption through oral cavity, avoids First pass metabolism .

Example:- codeine phosphate tablets, scopolamine HBr tablets, nitroglycerine tablets etc…

Buccal tablets Intended to be dissolved in

buccal pouch. Tablets are designed not to

disintegrate. It is placed near the opening of

parotid duct to provide the medium to dissolve the tablet.

Buccal tablets are most often used when replacement hormonal therapy is the goal, e.g., methyl testosterone, testosterone propionate.

Dental cones These tablets are designed to be

loosely packed in the empty socket remaining following a tooth extraction.

Main purpose behind the use of this tablet is either to prevent multiplication of bacteria in the socket by employing a slow releasing antibacterial compound or to reduce bleeding by an astringent or coagulant containing tablet.

It’s formulated to disslove or erode slowly in presence of a small volume of serum or fluid over 20-40 minutes period.

Vaginal tablets

Designed for vaginal administration in treatment of local vaginal infections, for systemic absorption and absorption into vaginal tissue.

Can be inserted with aid of appliantor

In the treatment of localized vaginal infections such as, Candida albicans, yeast and Haemophilus vaginalis.

Examples;- Cyclodextran formulations of hydrophilic drugs such as

amino-glycosides, beta-lactum antibiotics and peptides. propanolol.

Implants Designed for subcutaneous implantation by

surgical procedure where they are slowly absorbed over a period of month or a year.

Special injector with a hollow needle and plunger is used to administer the rod shaped tablet.

For other shapes surgery is used.

They are sterile formulation without excipients.

Mainly these tablets are prepared to deliver growth hormones to food producing animals.

Effervescent tablets Effervescent tablets are dropped into a

glass of water before administration during which carbon-dioxide is liberated. This facilitates tablet disintegration and drug dissolution; the tablet disintegration should complete within few minutes.

(Effervescence is a special mech. For disintegration) carbon-dioxide is created by the reaction between carbonate or bicarbonate and a weak acid such as citric acid or tartaric acid.

ADVANTAGES Rapid drug action e.g. analgesics and

antacids. Facilitate drug intake, e.g. vitamins.

Hypodermic tablets They are intended to be added in WFI

of sterile water to form a clear solution which is to be injected parenetrally.

Widely used by rural physician due to its portability.

Can be used for medicaments whose stability in water is very poor

They use in this manner should be discouraged. Since resulting solutions are not sterile.

Tablet Triturates

They are small, usually cylindrical, molded or compressed tablets containing small amounts of usually potent drugs.

Only a minimal pressure is applied during their manufacturing, since they must be readily and completely soluble in water.

Tablet design and formulation TABLET DESIGN

The objective of design & manufacture of the compressed tablet is to deliver orally the correct amount of drug in the proper form, at or over the proper time & in the desired location.

Aside from the physical or chemical properties of the medicinal agents, the actual physical design, manufacturing process, and complete chemical makeup of the tablet can have a profound effect on the efficacy of the drug being administerd.

Formulation components

In addition to the active ingredients, tablet contains a number of inert materials known as additives or excipients.

Different types of excipients are :-

Diluents. Binders & Adhesives. Disintegrents. Lubricants & Glidants. Coloring agents. Flavoring agents. Sweetening agents.

Excipients :- functions

Impart weight, accuracy & volume (it allows accuracy of dose).

Improve solubility. Increase stability. Enhance bioavailability. Modifying drug release. Increase patient acceptability. Facilitate dosage form design.

Diluents

They are used to make required bulk of the tablet when the drug dosage itself is inadequate to produce bulk.

It provide better tablet properties such as improve cohesion, to promote flow.

DESIRED PROPERTIES:- Non-toxic. Cost must be low. Commercially available in acceptable grade. Must be chemically & physically stable. Do not alter the bioavailability of the drug. Must be color compatible.

Commonly used diluents

Lactose-anhydrous and spray dried lactose. Directly compresssed starch- Sta Rx1500. Hydrolyzed starch- Emdex and celutab. Microcrystalline cellulose- Avicel (PH 101 & PH

102). Dibasic calcium phosphate dehydrate. Calcium sulphate dihydrate. Mannitol. Sorbitol. Sucrose- sugartab, DiPac, Nutab Dextrose.

Binders & Adhesives These materials are added either dry or wet-

form to granules or to form cohesive compacts for directly compressed tablet.

Example:- Acacia, Tragacanth – solution for 10-25% conc. Cellulose derivatives- Methyl cellulose, Hydroxy

propyl cellulose. Gelatin-10-20% solution. Polyvinyl pyrrolidine (PVP)- 2% solution. Starch paste- 10-20% solution. Sodium Alginate. Sorbitol.

Disintegrants

Added to a tablet formulation to facilitate its breaking or disintegration when it contacts in water in the GIT.

Example:- Starch- 5-20% of tablet weight. Starch derivative- Primogel & Explotab (1-

8%). Clays- Veegum HV, Bentonite 10% level in

colored tablet. Cellulose. Alginate.

Lubricants & Glidants

Lubricants are intended to prevent adhesion of the tablet materials to the surface of dies and punches, reduce inter particle friction & may improve the rate of flow of the tablet granulation.

Glidants are intended to promote flow of granules or powder material by reducing the friction between the particles.

Examples:- Lubricants:- stearic acid, mag. Stearate, talc,

PEG, Surfactants. Glidants:- corn starch, talc, silica derivatives:-

colloidal silicas, syloid, etc.

Coloring Agents

The use of colors & dyes in a tablet has three purposes:-

i) Masking of off color drugs ii) Product identification. iii)Production of more elegant product. All coloring agents must be approved & certified

by FDA. Two forms of colors are used in tablet preparation-

FD & C And D&C dyes. These dyes are applied as a solution in

the granulating agents or lake form of these dyes. Examples:- FD&C yellow 6-sunset yellow, FD&C

Green 3- Fast Green, etc

Flavoring agents

For chewable tablet- flavor oil are used

Sweetning agents For chewable tablets: e,g;-mannitol, sugar, etc. Saccharine(artificial): 500 times sweeter then

sucrose. Aspartame

Evaluation test i) General Appearance. ii) Organoleptic properties. iii) Weight Variation. iv) Content uniformity. v) Hardness. vi) Friability. vii) Dissolution test. viii) Disintegration test

General Appearance Size & shape :- Thickness : ±5% of standard value. Thickness of tablet is measured with a micrometer.

Organoleptic Properties Color: color of product must be uniform (no

mottling). Instruments used:- Reflectance spectrophotometer. Tristimulus colorimetry. Micro-reflectance photometer. odor: (e.g. film coated tablets). Taste: (e.g. chewable tablet).

Weight Variation 20 tablets weighed ——› Average individual

weight. No more than 2 tablets are outside of limit. IP % USP

Less than 85mg

±10% Weighing 130 mg or less

85mg-250mg ± 7.5% Weighing 130-324mg

Greater than 250mg

±5% Weighing 324 mg or more

Content Uniformity

30 Tablets are selected and 10 are assayed individually.

9 of the 10 tablets must contain not less than 85% or more than 115% of the labeled drug content.

Hardness test It is the force required to break a tablet in a

diametric compression also called tablet crushing strength.

The force required to break the tablet is measured in kg & usually 4kg is considered to be minimum for satisfactory tablets.

Instruments used The Monsanto hardness tester

The strong- cobb apparatus

Pfizer tester

Friability Resistance shown by the tablet during

packaging and transhipment. 20 tablets are weighed & placed in

apparatus-Roche Friabilator ——› Revolution at 25 rpm for 4 min(100 revolution) ——› Dropping from 6 inches.

The tablets are weighed & the weight compared with the initial weight.

% Friability =initial weight – final weight x 100

initial weight

limit :- 0.5-1%

Dissolution test It is defined as the amount

of drug substance that goes into solution per unit time under standardized conditions of liquid/solid interface, temperature and solvent composition.

It is carried out in:-i) USP dissolution apparatus

type I (basket type)ii) USP dissolution apparatus

type II (Paddle type)

Disintegration test 6 test tubes & 3 inch long ——› 10 mesh

screen —› 1L beaker of water(0.1N HCL) simulated gastric fluid or simulated intestinal fluid ——› temp 37±2ºC ——› up & down from 5-6 cm ——› Frequency- 28-32 cycle/minute.

tablet should remain 2.5 cm below the surface of liquid on their upward movement & same for downward movement.

uncoated tablets:- as low as 5 min Majority of tablets has disintegration time

of 30 min. Enteric coated:- simulated gastric fluid:- no

evidence of disintegration after one hour. simulated intestinal fluid:-

2hrs + time specific in monographs.

Quality control of coated tablet After coating, the tablets should be inspected &

tested for appearance such as color, size & any physical defects.

In-vitro performance of the coated product is evaluated by disintegration & dissolution testing.

Crushing strength of coated tablets can be determined with the tablet hardness tester.

Adhesion tests with tensile-strength testers have been used to measure the force required to peel the film from the tablet surface.

Additional testing of coated tablets may also includes tests for resistance to chipping & cracking during handling.

METHODS & DEVICES FOR THESE TESTS ARE SIMILAR TO THOSE USED FOR UNCOATED TABLETS.

Lieberman’s Lachman;”The theory and practice of Indusdtrial Pharmacy”,CBS publishers & distributors pvt ltd, fourth edition, pp:- 449-522