Module 1 - Tablets ( Part 2)

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NIPER JEE Preparation Pharmaceutics Tablets Part 2

In the part 2 of this module, we will learn the following on the tablets. In this module, we will study only important points for NIPER JEE. Kindly read the references given at the end, if you need more comprehensive information on any topic.

Learning objectives:

Manufacture of tablets

Machines used to manufacture tablets are called tablet presses.

Roles of different parts of tablet presses

Turrets: It holds the upper and lower punches

Wipe off blades: To remove excess granulation

Fette machine

Used for the production of suppositories.

Used for the compression of low melting point substances such as waxes

Direct compression

* Tablets compressed directly from powder mixture of API and excipients

* It involves blending and compression steps

* Have lesser steps

* Suitable for heat and water sensitive drugs

* Economical and cheaper technology

Disadvantages

* Not suitable for low and high dose drugs

* High dose drugs may not be directly compressible - to make them compressible large amount of diluents is required making them bulky and costly

* Low dose drugs- problems in uniform distribution of drug

* Interaction of direct compression diluents and drugs

* A static charge sometime buildup during mixing and screening process which further make the uniform distribution of drug a challenge.

Dry granulation

Purpose of granulation: size enlargement process which converts particles into large free flowing and compressible granules

Dry granulation- powder mixture is compressed without the use of heat and solvent

Two methods for dry granulation

Slugging: powder is pre-compressed and slug is further milled to yield the granules.

Purpose of slugging

Slugging results in strengthening of bongs that make friability free tablets

Rollar compactation:

It is used to produce granules on larger scale

Chilsonator roller is most commonly used

Rollar compression is generally preferred method over slugging method due to increased production capacity and greater control over compactation pressure.

Advantages of dry granulation

* Suitable for moisture sensitive and heat sensitive drugs

* Improved disintegration time as binder is not used in dry granulation

Disadvantage of dry granulation

Requires a specialized machine for precompression such as chilsonater

Uniform color distribution can't be achieved

Preferred method of precompression

Formulation for dry granulation

The commonly used diluents are:

Lactose

Dextrose

sucrose

MCC

Calcium phosphate

Sta-Rx (modified starch)

Wet granulation

* Most widely used method of granulation

* The granulation is facilitated by a binder

* Wet granuation involves addition of binder solution, suspension or slurry to the powder mixture

Disadvantage

* Costly process because of labor, time, equipment, energy and space requirements.

* Not suitable for moisture sensitive drugs

Role of drying process

To remove the solvents and moisture used in wet granulation

List of equipments for wet granulation

High shear granuation

* Littleford lodgie granulator

* Littleford lodgie MGT granulator

* Diosna granulator

* Gral mixer

Granulator with drying facility

* Fluidized bed granulator

* Day nauta mixer processor

* Double cone or twin shell processor

* Topo granulator

Special granulator

* Roto granulator

* Marumerizer

Excipients

Lactose is most widely used in tablet production

Anhydrous lactose does not undergo Maillard reaction with amine drugs

Maillard reaction: reaction between amino acids and reducing sugar

Two grades of lactose:

60-80 mesh (coarse)

80-100 mesh (regular grade)

Spray dried lactose darkens in presence of amine and moisture due to the presence of Furaldehyde

Diluents

Lactose

Sta-Rx 1500- directly compressible starch

* Used as diuent, binder and disintegrating agent

* Contain 10% water

Hydrolyzed starch

* Embdex

* Celutab

* Both contain 90-92% dextrose and 3-5% maltose

Dextrose- Cerelose

Mannitol

* Expensive sugar

* Suitable for chewable tablets

* Poor flow characteristics- need large amount of lubricants

Sucrose or sugar - used as direct compressible diluent

* Sugar tab: 90-93% sugar + 7-10 % invert sugar

* Dipac: 97% sugar + 3% dextrins

* Nutab: 95% sugar + 4% invert sugar with corn starch and magnesium stearate

Avicel : Micocrystalline cellulose

Two grades

PH101 for powders: 50 um particle size

PH102 for granules: 100 um particle size

Binders

To form the granules

Natural binders

* Acacia

* Tragacanth

* Gelatin

* Starch paste

* Alginic paste

* Cellulose

Synthetic

* Methyl cellulose

* Ethyl cellulose

* HPMC

* Hydroxyl methyl cellulose

* Sodium carboxymethly cellulose

* PVP

* PEG

Commonly used binders

* Starch 1500 - Partially pregelatinized maize starch

* Methocel-HPMC

* Walocel- Hydroxy propyl methyl cellulose

* Sugar is also used as binders

Disintegrants

They cause disintegration of tablets in GI tracts

Example: Starch- 5-20% of tablet weight

Starch derivative - Primogel and Explotab (1-8%)

Clays- Veegum HV, bentonite 10% level in colored tablet only

Cellulose derivatives- Ac- Di-Sol (sodium carboxy methyl cellulose)

Other: cross-linked Polyvinylpyrrolidone

Superdisintegrants

Swells 10 times of their size in water in 30 sec

Cross carmellose: cross linked cellulose

Cross povidone: cross linked povidone

Sodium starch glycolate: cross linked starch

Ethyl cellulose may retard disintegration and dissolution time of tablet

Lubricants, anti-adherents and glidants

Lubricants: decrease the friction between walls of tablet and die cavity during ejection process

Anti-adherents: decrease the sticking of granule or powder to the punches and dies

Glidants: increase the flow properties of granules by decreasing the friction

Most commonly used lubricants

* Stearic acid and stearic acid salts such as calcium and magnesium salts

* Stearic acid is less effective lubricant than its salts

* Talc- second most commonly used

* Hydrocarbon oils

* High molecular weight PEG

* Surfactants

Anti-adherents

* Talc

* Mag stearate

* Starch

* Colloidal silica

Glidants/flow promoters

* Talc (5%)

* Starch (5-10%)

* Colloidal silica: Cab-o-sil

* Syloid

* Aerosil

* 0.25-3% conc

Colors

Lakes: dyes absorbed on hydrous oxides and used as dry powders for coloring

Flavors

For chewable tablets

Sweetening agents

Saccharine- 500 times sweeter than sucrose

Disadvantage: bitter after taste and carcinogenic

Aspartame: Unstable in water

Processing problems

Capping: it is complete or partial separation of upper or lower layers of tablets.

Lamination: it is separation of tablets into multiple layers.

Reason: due to entrapment of air in granules.

Prevention:

* Precompression

* Slowing the tabletting rate

* Reducing the final compression pressure

* Flat punches may prevent the capping and lamination

* Less moisture in granules result in capping and lamination-increase the amount of binder

* Correcting the incorrect setting of tools of press such as dies, punches and sweep-off blades

Picking and sticking

Sticking is when the granules are sticked to the punches instead of creating a uniform tablet.

Picking occurs when the granules or tablet sticks to the engraving or embossing on the punches.

Small enclosed alphabets such as B, A, O, D, Q on punches pose special challenges in producing a sticking free tablet.

Chipping: due to severe sticking of material at the punches, produces tablets with rough edges.

Prevention

* Alphabets can be designed as large as possible

* Chromium plated punches to produce a smooth surface

* Use of lubricants such as silica, magnesium stearate

* Low molecular weight lubricants such as polyethylene glycol , stearic acid may promote sticking as they melt due heat of compression

* Reducing the excessive moisture in granules

Mottling

Unequal distribution of color in a tablet.

Prevention

* Change in solvent system

* Reducing drying temperature

* Reducing particle size of powders

* Using of binders such as acacia and tragacanth

Poor flow

Rat holing and bridging in the feed frame. The flow of powder in feed frame can be increased by using glidants such as talc or colloidal silica.

Double impression

* Free rotation of either upper punch or lower punch during ejection of a tablet.

* Use keying in tooling, i.e. inset a key alongside of the punch, so that it fits the punch and prevents punch rotation.

* Newer presses have anti-turning devices, which prevent punch rotation.

References and further reading

Banker, G. S., & Anderson, N. R. (1991). The theory and practice of industrial pharmacy; Lachman, L. 3rd edition.

Remington, J. P. (2006). Remington: The science and practice of pharmacy (Vol. 1). D. B. Troy, & P. Beringer (Eds.). Lippincott Williams & Wilkins.

http://www.techceuticals.com/Article_Tablet_Press_Operation_Sticking_10_...

http://www.pharmainfo.net/tablet-ruling-dosage-form-years/problems-tablet-manufacture-and-related-remedies

http://www.pharmainfo.net/tablet-ruling-dosage-form-years/problems-tablet-manufacture-and-related-remedies/tablet-double-impression

http://www.pharmainfo.net/ebooks/tablet-ruling-dosage-form-years

About the Author

Kapil Pal's picture
Author: Kapil Pal

Kapil Pal holds a Bachelor's and Master's degree in Pharmacy. He is a registered pharmacist based in India. He had earned a national scholarship to study at the prestigious National Institute of Pharmaceutical Education and Research, Punjab, India. He has a lot of medical articles to his credit, published in the Drug Today Medical Times, India. He authored three chapters for the Encyclopaedia on Pharmacology and Society, Sage Publications, which is currently in the publishing stage. He has also published many business cases in Sage Publications.He has also authored a book on Ebola Virus Disease, titled Ebola: Is There Any Cure? He is currently working in a UK based pharmaceutical consultancy company.

Connect with Kapil Pal at: kapilpal1561988@gmail.com

http://www.pharmainfo.net/Kapil-Pal

 

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