GENERAL TIPS Types of Tablet:-

IP BP USPUncoated Uncoated Compressed/moldedFilm Coated Coated Plain CoatedEnteric Coated Gastro Resistent (Enteric

Coated)Delayed Release

Dispersible Tablet Dispersible Tablet Dispersible TabletModified Release Tablet Modified Release Tablet Exteded Release TabletSoluble Tablet Soluble Tablet Soluble TabletEffervescent Tablet Effervescent Tablet Effervescent TabletFor use in mouth (Chewable, Lozenges, Sublingual)

For use in mouth (Chewable, Lozenges, Sublingual)

Chewable/Buccal, Sublingual

Orodispersible Orodispersible Orodispersible

Standards for Tablets:-IP BP USPContent of Active Ingredient

Content of Active Ingredient

Content of Active Ingredient

Uniformity of weight Uniformity of weight Weight VariationUniformity of Content Uniformity of Content Uniformity of ContentDT DT DTDissolution Dissolution Dissolution

1) Content of Active Ingredient: - 1) Assay of Active 2) 20 tabs: - Limits 90% to 110%

2) Uniformity of Weight/Wt Variation:- 20 tabs, calculate avg. wt NMT 2 deviate, none twice the limits.

Weight Variation Limits:-1) For Tablets 2) For Capsule:-

IP/BP Limit USP80 mg or less 10% 130mg or lessMore than 80mg or Less than 250mg

7.5% 130mg to 324mg

250mg or more 5% More than 324mg

Friability Test:- This test is additional to check crushing strength of tablet by this test one can check Capping &/or Lamination. USP limit is 0.5 to 1%. Rotation: - 25 rpm or 100 rotations in 4 min.

IP LimitLess than 300mg 10%300mg or More 7.5%

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USP 29-now <905>Uniformity of Dosage Units≥ 25 mg & 25% of active ingredient

Uniformity of Content or Content Uniformity:-IP: - Active less than 10mg or 10%,BP:- Active less than 2 mg or 2%,USP:- Active less than 25mg or 25%.-10 tabs limit NMT 1 tab deviate 85 – 115% & none outside 75 – 125% of the Avg value/IP/BP/USP (Relative Standard Deviation less than or equal to 6%),- If 2 or 3 individual values are outside the limits 85 – 115% of the Avg value, & none outside 75 – 125% repeat for 20 tabs.- Complies when 30 tabs NMT 3 of the individual values are outside the limit 85 – 115% of the Avg value, and none outside 75 – 125%.

Disintegration Time:- Uncoated Tablet NMT 15 min, in water with Disc 370C ± 20CCoated Tablet NMT 30 min, In water with Disc for Film Coated Tab, and

NMT 60 min Other than Film coated tabletEnteric Coated Tab Intact for 1 hr in 0.1 N HCl & disintegrate within 2 hr in Mixed

6.8 Phosphate buffer. According to USP 1 hr in Simulated gastric fluid, then in Simulated Intestinal Fluid.

Dispersible/Soluble Within 3 min in water at 250C ± 10C (IP) & 15 – 250C (BP)Orodispersible Within 1 minEffervescent Tab 5 min in 250 ml water at 20 – 300C (IP) & 5 min in 200 ml

water at 15-250C (BP)Buccal & Sublingual Not Applicable but dissolve within 15 – 30 min.

DT Apparatus:- Mesh Apperture:- 2mm (#10), Cycles:- 28 – 32 cycles/min, 50 – 60 mm distance from bottom & top, Temp of water 370C ± 20C. If 1 or 2 tabs fail, repeat for 12 tabs.

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Solubility:-

BP SOLUBILITIES

Compressibility Index (Carr’s Index):- Angle of Repose:-Tapped Density – Bulk Density x 100 θ = tan-1(h/r)

Tapped Density

Very soluble less than 1 partFreely soluble from 1 to 10 partsSoluble from 10 to 30 partsSparingly soluble from 30 to 100 partsSlightly soluble from 100 to 1000 partsVery slightly soluble from 1000 to 10,000 partsPractically insoluble more than 10,000 partsApproximate quantity of solvent by volume for one part of soluble by weight.  For example, 1g of a very soluble substance dissolves in less than 1ml of solvent (1gm/ml).

Flow property C.I (%) Hausner ratioExcellent ≤10 1.00 – 1.11Good 11 – 15 1.12 – 1.18Fair 16 – 20 1.19 – 1.25Passable 21 – 25 1.26 – 1.34Poor 26 – 31 1.35 – 1.45Very poor 32 – 37 1.46 – 1.59Very, very poor >38 >1.60

Flow property Angle of repose (degrees)Excellent 25 – 30Good 31 – 35Fair-aid not needed 36 – 40Passable – may hang up 41 – 45Poor – must agitate, vibrate

46 – 55

Very poor 56 – 65Very, very poor >66

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Bioavailability:- The rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action. For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.ANDA - Abbreviated New Drug Application.IND – Investigational New Drug Application.NDA – New Drug Application.

According to the BCS, drug substances are classified as follows:

Class I - High Solubility, High PermeabilityClass II - High Permeability, Low SolubilityClass III -High Solubility, Low Permeability Class IV - , Low Solubility Low Permeability

A drug substance is considered HIGHLY SOLUBLE when the highest dose strength is soluble in < 250 ml water over a pH range of 1 to 7.5.

A drug substance is considered HIGHLY PERMEABLE when the extent of absorption in humans is determined to be > 90% of an administered dose, based on mass-balance or in comparison to an intravenous reference dose.

A drug product is considered to be RAPIDLY DISSOLVING when > 85% of the labeled amount of drug substance dissolves within 30 minutes using USP apparatus I or II in a volume of < 900 ml buffer solutions.

DISSOLUTION DETERMINATION

USP apparatus I (basket) at 100 rpm or USP apparatus II (paddle) at 50 rpm. Dissolution media (900 ml): 0.1 N HCl or simulated gastric fluid, pH 4.5 buffer,

and pH 6.8 buffer or simulated intestinal fluid. Compare dissolution profiles of test and reference products using a similarity

factor (f2).

AN ARRAY OF TABLET TYPES

Immediate Release Uncoated Tablets: Usually no taste/stability issues.

Coated Tablets: For taste/stability/identification (coated with  water-soluble/dispersible polymer–mixture of hydroxypropyl cellulose/hydroxypropylmethyl cellulose); coating readily ruptures in GI tract.

Enteric-Coated Tablets: For drugs inactivated or destroyed in the stomach or for those causing irritation to the gastric mucosa; tablet passes through the stomach but disintegrates in the intestines where absorption takes place. Excipients used for enteric coating include cellulose acetate phthalate, mixtures of fats and fatty acids, etc.

Multiple Compressed Tablets: Multiple-layered tablets manufactured by using more

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than one compression cycle. Each layer contains a different drug and each may be colored differently.

Controlled Release Tablets: Improved therapy, less toxicity, improved patient compliance—using polymers such as methacrylates.

Sublingual Tablets: Small, flat ovals such as nitroglycerin. They are ideal tablets for absorption of drugs which are destroyed by gastric juice or undergo first pass metabolism.

Chewable Tablets: Disintegrate rapidly when chewed for patients with swallowing difficulty (children, elderly) and when there is no access to water. Most commonly used for multiple vitamins and antacids.

Effervescent Tablets: In addition to the active, this product form contains sodium bicarbonate and citric acid. When water is added the ensuing chemical reaction forms carbon dioxide, which acts as a disintegrant and produces effervescence that hastens dissolution (antacids).

Official Standards as per I.P. / B.P. / U.S.P.

COMPARISON OF DIFFERENT PHARMACOPOEIAL QUALITY CONTROL TESTS

PHARMACOPOEIAS TYPE OF TABLET

TESTS TO BE PERFORMED

BRITISH PHARMACOPOEIA

For all tablets

Content of active ingredients

DisintegrationUniformity of content

Labeling

Uncoated tabletDisintegration testUniformity of weight

Effervescent tabletDisintegration testUniformity of weight

Coated tablet Disintegration testUniformity of weight

Gastro resistant tablet

Disintegration test

Modified release tablet

Uniformity of weight

Tablet for use in mouth

Uniformity of weight

Soluble tablet Disintegration testUniformity of weight

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Dispersible tablet

Disintegration test

Uniformity of dispersion

Uniformity of weight

INDIAN PHARMACOPOEIA

Uncoated tablet

Uniformity of container content

Content of active ingredientUniformity of weightUniformity of content

Disintegration testEnteric coated tablet Disintegration test

Dispersible tabletUniformity of dispersionDisintegration

Soluble tablet Disintegration test

Effervescent tabletDisintegration/ Dissolution / Dispersiontest

UNITED STATES PHARMACOPOEIA

Physical tests applicable to tablet formulation

Bulk density /Tapped density of powder

Powder finenessLoss on dryingDisintegration testTablet friabilityDissolution testDrug release testingUniformity of dosage formContainer permeation test

Labeling of inactive ingredients

Tablet Problems:-

Capping:- ‘Capping’ is the term used, when the upper or lower segment of the tablet separates horizontally, either partially or completely from the main body of a tablet and comes off as a cap, during ejection from the tablet press, or during subsequent handling.

Lamination / Laminating:- Definition: ‘Lamination’ is the separation of a tablet into two or more distinct horizontal layers.

Chipping:- ‘Chipping’ is defined as the breaking of tablet edges, while the tablet leaves the press or during subsequent handling and coating operations.

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Cracking:- Small, fine cracks observed on the upper and lower central surface of tablets, or very rarely on the sidewall are referred to as ‘Cracks’.

Sticking / Filming:- ‘Sticking’ refers to the tablet material adhering to the die wall.Filming is a slow form of sticking and is largely due to excess moisture in the granulation.

Picking:- ‘Picking’ is the term used when a small amount of material from a tablet is sticking to and being removed off from the tablet-surface by a punch face.The problem is more prevalent on the upper punch faces than on the lower ones. The problem worsens, if tablets are repeatedly manufactured in this station of tooling because of the more and more material getting added to the already stuck material on the punch face.

Mottling:- ‘Mottling’ is the term used to describe an unequal distribution of colour on a tablet, with light or dark spots standing out in an otherwise uniform surface.

Double impression:- ‘Double Impression’ involves only those punches, which have a monogram or other engraving on them.

Problems for tablet coating:-

Blistering:- It is local detachment of film from the substrate forming blister.

Chipping: It is defect where the film becomes chipped and dented, usually at the edges of the tablet.

Cratering: It is defect of film coating whereby volcanic-like craters appears exposing the tablet surface.

Picking: It is defect where isolated areas of film are pulled away from the surface when the tablet sticks together and then part.

Pitting: It is defect whereby pits occur in the surface of a tablet core without any visible disruption of the film coating.

Blooming: It is defect where coating becomes dull immediately or after prolonged storage at high temperatures.

Blushing: It is defect best described as whitish specks or haziness in the film.

Colour variation: A defect which involves variation in colour of the film.

Infilling: It is defect that renders the intagliations indistinctness.

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Orange peel/Roughness: It is surface defect resulting in the film being rough and nonglossy. Appearance is similar to that of an orange.

Cracking/Splitting: It is defect in which the film either cracks across the crown of the tablet (cracking) or splits around the edges of the tablet (Splitting).

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