TABLETS

    Short notes on tablets I

In this first article on tablets I am going to provide some important points regarding tablet formulation.  

ü  I: Advantages, disadvantages, tablet defects and the excipients used in the formulation of tablets

ü  II: Evaluationparameters and types & classes of tablets.

Second part of this topic will be provided in the next post. So, for short notes on second point please refer the next post.

Let’s start with the first point in this topic.

ADVANTAGES OF TABLETS

Oral route of administration is the most preferred route for the administration of drugs for their systemic effects. Tablets are mostly preferred for this due to following advantages:
·         Unit dosage forms
·         Greatest dose precision
·         Least content variability
·         Lowest cost
·         The lightest and the most compact oral dosage forms
·         Easy transportation as compared to liquids
·         Product identification is easy
·         Can be formulated as modified drug release product
·         Better suited to large-scale production
·         Best chemical, mechanical and microbiological stability

DISADVANTAGES OF TABLETS

·         Properties of some drugs to resist compression due to low-density and flocculant nature.

·        Drugs having characteristics like poor wettability, large dosage and sow dissolution are difficult     to formulate as tablets.

·   Drugs having bitter taste, objectionable odor and moisture absorption tendency need encapsulation.  In this case capsule is a better choice.  

TABLET DEFECTS 

Tablet defects	Description
Mottling	Non-uniformity of colors of tablets. Uneven distribution of color particles in tablet.
Capping	Partial or complete separation of top or bottom crowns of tablet from main body.
Lamination	Separation of a tablet into two or more distinct layers.
Sticking	Tablet material adhering to die wall
Picking	Surface material of tablet sticking to & being removed (picked) by punch.

EXCIPIENTS USED IN THE TABLET FORMULATION

Excipients are the inert materials which assist in the formulation of any dosage form with desired properties. In the formulation of tablets excipients having properties such as (a) diluent, (b) binder, (c) disintegrant and (d) lubricants are used.

Let’s see some important points on which questions were asked in previous year GPAT examinations. (and of course some new points!)

DILUENTS

Also known as fillers and bulking agents.

Primary role: To produce bulk (added when drug dose is inadequate for compression).

Important points regarding diluents:

1.      If calcium salt (such as calcium phosphate) is used as diluent in the tetracycline product, what will happen?

This condition was noticed while marketing of tetracycline antibiotic tablet where drug showed less than half the bioavailability of standard product.

Tetracycline + Calcium salt àThis divalent cation (Ca⁺²) binds to the active site of tetracycline and causes inactivation à    reduction in absorption of drug and less or no therapeutic effect.

2.      Maillard reaction: Also known as browning reaction.

Lactose is a commonly used diluent.

When it was used as a diluent for formulation of amine drugs, in presence of metal stearate lubricant (magnesium stearate), the product (tablet) showed brown discoloration with time.

Amine drugs (API) + Lactose (diluent) + metal stearate (lubricant)  à  Brown discoloration of tablet.

3.      Hydrous lactose: Undergoes Maillard reaction

Anhydrous lactose: Does not undergo Maillard reaction.

4.      Difference between hydrous and anhydrous

Hydrous: Compounds/salts that contain bound water as water of crystallization.

Anhydrous: No bound water. Anhydrous compounds are proe to moisture absorption when exposed to humidity.

5.      When wet granulation is employedà if lactose is used then its hydrous form is preferred.

Direct compression àSpray-dried lactose.

6.      Directly compressible starches à Sta-Rx 1500, Emdex, Celutab.

7.      Diluents used in chewable tablets à Mannitol, Emdex, Celutab, Sucrose. 

8.      Sucrose based diluents:

i)                  Sugartab (90 to 93% sucrose + 7 to 10% invert sugar)

ii)                DiPac (97% sucrose + 3% modified dextrins)

iii)              NuTab (95% Sucrose + 4% invert sugar + small amount of corn starch and magnesium stearate)

9.      Avicel à Microcrystalline cellulose

Grades à PH 101: powder

                  PH 102: granules

BINDERS AND ADHESIVES

Dry form à to form cohesive compacts while direct compression.

Liquid from à to form granules.

1.      Natural gums: Acacia, Tragacanth (10-25% aqueous solutions are used).

Acacia+Tragacanth or alone each compound.

Gelatin + Acacia.

2.      Most common granulating agent: Starch paste.

Liquid glucose (50% aqueous solution)

Sucrose solution (50-74% concentration)

3.  Modified natural polymers: Alginate and cellulose derivatives (Methylcellulose, Hydroxypopyl methylcellulose & Hydroxypropyl cellulose)

4.      Direct compression à dry powders à binder capabilities

Granulation à aqueous solutions à adhesive properties

DISINTEGRANTS

 Role: Promote disintegration (breaking) of tablet upon contact with water/ gastrointestinal fluids.

Mechanism: Draws water inside of tablet  à swelling àbursting of tablet into fragments à dissolution of fragments à absorption of drug

1.      Starch à 5 to 20% of tablet weight

2.      Substituted carboxymethyl starches à Pimogel and Explotab

(used in concentration 1 to 8%, Optimum concentration is 4%)

3.      Pre-gelatinized starches à 5%

4.      Clays à Veegum HV and Bentonite (10%)

5.      Ac-Di-Sol à an internally cross-linked form of Sodium Carboxymethyl Cellulose.

LUBRICANTS, ANTIADHERENTS AND GLIDANTS

• Lubricants: These reduce friction between surface of tablet and die wall during tablet ejection.
• Antiadherents: Reduce sticking/ adhesion of powder or granules to the punch and die.
• Glidants: Reduce friction between particles and helps in easy flow of granules or powder.
• 1.      Lubricant property: Stearic acid salts > Stearic acid
• 2.      Colloidal silica: Cab-O-Sil, Syloid or Aerosil

MATERIAL	PROBLEM
Mineral oil (Sprayed on granules)	Produce oil spots
Talc	Traces of iron. Causes breakdown of some dugs due to catalytic effect of iron.

COLORS, FLAVORS AND SWEETENERS

COLORS:

Role    à disguising of off-color drugs

            à product identification

è Production of elegant product

Dyes: FD&C and D&C dyes à applied as solutions

Lakes: Employed as dry powders

FLAVOURS:

è Limited to chewable tablets & tablets that are intended to dissolve in mouth.

è Water soluble flavours à poor stability à little acceptance

è Flavour oils à 0.5 to 0.75 %

SWEETENERS:

è Used in chewable tablets.

è Mannitol à 72% as sweet as Sucrose

è Saccharin à 500 times sweeter than Sucrose

Disadvantage: Bitter aftertaste and carcinogenic.

è Aspartame à 200 times sweeter than sucrose

Disadvantage: unstable in presence of moisture.

Reference: The theory and Practice of Industrial Pharmacy by Lachman & Liberman.

This is what I currently got for you guys. I will update this article with new information regularly.

If you have any questions regarding this article or suggestion, then feel free to leave a comment below.