TABLETSManufacturing, Equipment and Quality Control.Anirban Saha

M.Pharm (Pharmaceutics)Semester- 1Amity University.

AMITY INSTITUTE OF PHARMACY

In early days, most of the tablets required granulation of the powdered Active Pharmaceutical Ingredient (API) and Excipients. At the availability of new excipients or modified form of old excipients and the invention of new tablet machinery or modification of old tablet machinery provided an ease in manufacturing of tablets by simple procedure of direct compression.

Amongst the techniques used to prepare tablets, direct compression is the most advanced technology. It involves only blending and compression. Thus offering advantage particularly in terms of speedy production. Because it requires fewer unit operations, less machinery, reduced number of personnel and considerably less processing time along with increased product stability.

Lubricants To reduce the friction during tablet ejection between

the walls of the tablet and the walls of the die cavity

Glidants Reducing friction between the particles To improve the flow properties of the granulations

Antiadherants To prevent adherence of the granules to the punch

faces and dieso Wetting agents Antioxidants Preservatives Coloring agents Flavoring agents

Direct compression

Dry granulation

Wet granulation

Hopper for holding and feeding granulation to be compressed

Dies that define the size and shape of the tablet Punches for compressing the granulation within

the dies Cam tracks for guiding the movement of the

punches Feeding mechanisms for moving granulation

from the hopper into the dies

Mechanism

Multi-station rotary presses

The head of the tablet machine that holds the upper punches, dies and lower punches in place rotates

As the head rotates, the punches are guided up and down by fixed cam tracks, which control the sequence of filling, compression and ejection.

The portions of the head that hold the upper and lower punches are called the upper an lower turrets

The portion holding the dies is called the die table The pull down cam (C) guides the lower punches

to the bottom, allowing the dies to overfill The punches then pass over a weight-control cam

(E), which reduces the fill in the dies to the desired amount

A swipe off blade (D) at the end of the feed frame removes the excess granulation and directs it around the turret and back into the front of the feed frame

The lower punches travel over the lower compression roll (F) while simultaneously the upper punches ride beneath the upper compression roll (G)

The upper punches enter a fixed distance into the dies, while the lower punches are raised to squeeze and compact the granulation within the dies

After the moment of compression, the upper punches are withdrawn as they follow the upper punch raising cam (H)

The lower punches ride up the cam (I) which brings the tablets flush with or slightly above the surface of the dies The tablets strike a sweep off blade affixed to the front of the feed frame (A) and slide down a chute into a receptacle

At the same time, the lower punches re-enter the pull down cam (C) and the cycle is repeated

Multi Station Rotary Press.

Principle- Multi Station Rotary Press.

Although tablet compressing machinery has undergone numerous mechanical modifications over the years, the compaction of materials between a pair of moving punches within a stationary die has remained unchanged.

Special adaptations of tablet machines allow for the compression of layered tablets and coated tablets.

Coating/Polishing:What are the problems

What are the equipment

Why do it

Blistering, chipping, cratering, picking, pitting

Color variation

Roughness

Pan (standard/perforated) Coating Machines

Fluidized Bed Coating Machines

Spray Coating Machines

Vacuum, Dip & Electrostatic Coating Machines

Enhance appearance and colour

Mask taste and odour (film/sugar)

Improve patient compliance

Improve stability

Impart enteric, delayed, controlled release properties

Tablet Coating Machines

In-process Checks :-

Parameter Frequency

Wt. of 20 tabs Every hour by production and every two hours by QA

Hardness, thickness, length, width Every hour by production, every two hours by QA

Wt. variation Every half hour by production and every hour by QA

DT Every half hour by production, every hour by QA

Mixing of granulation blend

GranulationBinder(s)

Preparation of binder solution

Drying

Milling

In Process Testing

Disintegrant

screening

screeningInitial Blending

lubricant screening Final Blending

Compression

SolventFilm coating agent Preparation

Film Coating of Tablets

WeightHardnessFriability

Complete Process :

Packaging and Labelling

Quality Control of Tablets

General Appearance:-Size, shape, and thickness: This is important to facilitate packaging

and to decide which tablet compressing machine to use.

-Organoleptic properties: which include color and odor of the

tablets.

Official Standards as per I.P Uncoated tablet:-Uniformity of container content-Content of active ingredient-Uniformity of weight-Uniformity of content-Disintegration test

Enteric coated tablet:-Disintegration test

Dispersible tablet:-Uniformity of dispersion-DisintegrationSoluble tablet:-Disintegration testEffervescent tablet:-Disintegration/ Dissolution / Dispersion

test

Official and unofficial tests: Non official tests:

Hardness (crushing strength): It is the load required to crush the tablet

when placed on its edge.

Factors Affecting the Hardness: Compression of the tablet and compressive

force. Amount of binder. (More binder ,more

hardness) Method of granulation in preparing the

tablet.

Friability: It is the tendency of tablets to powder, chip

or fragment and this can affect the elegance appearance, consumer acceptance of the tablet, and also add to tablet’s weight variation or content uniformity problems.

An instrument called friabilator is used to evaluate the ability of the tablet to withstand abrasion in packaging, handling, and shipping.

Procedure:1. Weigh 20 tab altogether = W1 2. Put these tablets in the friabilator and

adjust the instrument at 100 rpm

3. Weigh the 20 tablets (only the intact ones) = W2

4. Friability (% loss) = It must be less than

or equal to1% . But if more we do not reject the tablets as

this test is non-official.

Friabilator

Thickness Test :o Thickness is an unofficial test .

o Thickness of the tablet is inversely proportional to hardness

i.e. increase in hardness decrease the thickness & vice

versa.

o Thickness of tablet is measured by Vernier caliper.

o It is determined for 10 tablets. Vernier Caliper

Official Tests:Disintegration: It is the time required for the tablet to break

into particles, the disintegration test is a measure only of the time required under a given set of conditions for a group of tablets to disintegrate into particles.

The time of disintegration is a measure of the quality. This is because, for example, if the disintegration time is too high; it means that the tablet is too highly compressed or is not of pharmacopoeial quality.

Liquids used in disintegration : Water, Simulated gastric fluid (PH = 1.2 HCl), or Simulated intestinal fluid (PH = 7.5)

KH2PO4 (phosphate buffer) + enzyme +NaOH)

Disintegration Apparatus

Limits(Uncoated tablets) :

Medium Temperature Time limit

According to U.S.P.

Simulated gastric fluid

37°C Not exceed 30min

According to B.P.

water 37°C Not exceed 15min

Limits(Coated):

Weight Variation (Uniformity of weight) of tablets:

1. Weigh 20 tablet selected at random, each one individually . X1, X2, X3… Xz

2. Determine the average weight. X= (X1+X2 +X3+…+ X20)/20

Limits Weight of tablet 130 mg or less then

%error = ±10% · Weight of tablet 130-324 mg then

%error = ±7.5% · Weight of tablet 324 mg or more then

%error = ±5%

Dissolution TestDissolution is performed to check the percentage release

from the dosage forms i.e.tablet.

Tablet breaks down into small particles which offers a greater

surface area to the dissolving media.

Disintegration test does not give assurance that particles will

release drug in solution at an appropriate rate, that’s why

dissolution tests & it’s specifications developed for all tablet.

Dissolution Apparatus

TYPES OF DISSOLUTION APPARATUS :

1. USP Dissolution apparatus I ( Basket method)

A single tablet is placed in a small wire mesh basket attached to the

bottom of the shaft connected to a variable speed motor. The basket

is immersed in a dissolution medium (as specified in monograph)

contained in a 1000 ml flask. The flask is cylindrical with a

hemispherical bottom. The flask is maintained at 37 ± 0.50C by a

constant temperature bath. The motor is adjusted to turn at the

specified speed and sample of the fluid are withdrawn at intervals to

determine the amount of drug in solutions.

USP Dissolution Apparatus I

2. USP Dissolution apparatus II ( Paddle method)

It is same as apparatus-1, except the basket is replaced by a paddle.

The dosage form is allowed to sink to the bottom of the flask before

stirring. For dissolution test U.S.P. specifies the dissolution test

medium and volume, type of apparatus to be used, rpm of the shaft,

time limit of the test and assay procedure for. The test tolerance is

expressed as % of the labeled amount of drug dissolved in the time

limit. USP Dissolution Apparatus II

Dissolution testing and interpretation IP standards

Pharmaceutics. The science of dosage forms design. (M.E. Aulton)

Leon Lachman, The theory and practice of Industrial Pharmacy,3rd edition, page no.67-68,77-78,315-317,296-303.

Indian Pharmacopoeia-2010,Govt.Of India ministry of health & family welfare,6th edition.

References

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