11. Evaluation of Tablets

Chapter 7Evaluation of Paracetamol Tablets

EVALUATION OF PARACETAMOL TABLETS

Almost all Pharmacopoeias include some suitable standards

and tests to ensure the quality of tablets. The standards and

tests may be given as follows:

a. Thickness and diameter

b. Weight variation

c. Hardness

d. Friability

e. Drug content

f. Disintegration time

g. In- vitro dissolution and its Kinetics studies

A. THICKNESS AND DIAMETER (Lachman et al., 1990)

The thickness of individual tablets is measured with a

micrometer, which gives us information about the variation

between tablets. Tablet thickness should be within a ±5%

variation of a standard value. Any variation in thickness within a

particular lot of tablets or between manufacturer’s lots should

not be clear to the unaided eye for consumer acceptance of the

product. In addition, thickness should be controlled to smooth the

progress of packaging.

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Micrometer (tablet thickness)

B. WEIGHT VARIATION TEST (USP, 2000)

The weight variation test would be a satisfactory method

for determining drug content uniformity of drug distribution. In

practice this test is performed by taking 20 tablets, from a batch.

20 tablets are weighed at a time and the average weight is

taken. Then the tablet is weighed individually. The percentage

deviation can be determined by using the following formula. The

percentage deviation can be determined by using the following

formula.

% Deviation =

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Average Weight Percentage Difference

130 mg or less 10

More than 130 mg through 324 mg

7.5

More than 324 mg 5

C. HARDNESS TEST (USP, 2000)

The hardness of the tablet is important for drug products

that have bioavailability problem or that are sensitive to altered

dissolution release profiles as a function of the compressive force

employed. Tablet hardness is the force necessary to break the

tablet diametrically. Hardness is sometimes termed the tablet

crushing strength. To perform this test the tablets are located

between two anvils and force is applied to the anvils, and the

strength required to break the tablet is noted. If the tablet is too

hard, the disintegration time is long and cannot meet up the

dissolution specification, if its too soft, it cannot withstand

handling when dealing with processes such as coating or

packaging and shipping operations. The force with which the

tablet is broken is expressed in kilograms and a hardness of 4Kg

is usually well thought-out to be the minimum for satisfactory

tablets. Oral tablets have a hardness of 4 to 10kg ; but,

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hypodermic and chewable tablets have a hardness of 3 kg and

sustained release tablets have about 10-20 kg.

Pfzier hardness tester was used for measuring the

hardness of the formulated Paracetamol tablets. From each batch

3 tablets were taken at random and subjected to test. The mean

of these 3 tablets were calculated.

D. FRIABILITY TEST (USP, 2000)

It is a measure of tablet strength. It is frequently measured

using Roche friabilator.

The normal revolution of this friabilator is 25rpm. The

friability is determined using the following formula.

F = 100 × (1-w/w0)

Where w0 = weight of tablets before friability

w = weight of tablets after friability

It is expressed in percentage. For conventionally

compressed tablets, the limit is 0.5% to 1% of their weight,

chewable tablet have high friability values. When capping is

observed on friability testing the tablet should not be considered

for commercials use.

E. WETTING TIME (Gohel et al., 2004)

A circular tissue paper of 10cm diameter were placed in a

Petri dish having an internal diameter of 10 cm. 10 ml of water

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containing methylene blue (10% w/w) was added to the Petri

dish. The tablet was carefully placed in the centre of the Petri

dish and the time taken for the water to reach the upper surface

of the tablets was known as wetting time.

F. DISINTEGRATION TEST (USP, 2000)

Disintegration is the state in which no residue of the unit

under test is leftover on the screen or, if a residue remains, it

consists of disintegrated parts of tablets component parts such

as insoluble coating of tablets or of capsule shell, or of any

melted fatty substance from pessary or suppository.

The fragmentation of a tablet into small fragments or

granules is called disintegration. The first step to form a solution

of the drug is disintegration. The time taken for disintegration is

determined by disintegrating apparatus. The machine is operated

at 28-32 cycles/min through a distance of 50-60mm. Place 6

tablets in apparatus (i.e., in tubes of basket), add disc to each

tube and operate the apparatus. At the end of the 15min all the

tablets should disintegrate, completely without leaving any

residue in the basket. Where as for other coated tablets the

disintegration time will vary accordingly.

G. DRUG CONTENT (IP, 2007)

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20 tablets were weighed and powdered. A quantity of

powder containing 0.15 g of Paracetamol was added to 0.1 M

NaOH, diluted with 100 ml of water. It was shaken for 15 minutes

and sufficient water was added to produce 200 ml. 10 ml of the

filtrate was diluted to 100 ml with water. Then 10 ml of the

resulting solution was added to 10 ml of 0.1 M NaOH, finally

diluted to 100 ml with water. The absorbance was measured at

maximum of 257 nm. Calculate the content of C5H9N02 taking 715

as the value of A (1%, 1cm) at maximum at 257 nm.

H. DISSOLUTION (USP, 2000)

Dissolution is the method by which a solid solute enters a

solution. Two objectives in the development of in-vitro dissolution

tests are to show (1) that drug release from the tablet is as close

as possible to 100% and (2) that the rate of drug release is

uniform batch to batch and is the same as the release rate from

those batches proven to be bioavailable and clinically effective.

Dissolution was carried out using USP dissolution apparatus

II (Rotating paddle apparatus). Dissolution of tablets was carried

out in 900 ml dissolution medium. The dissolution medium for

Paracetamol tablet was phosphate buffer pH 5.8. The

temperature of the dissolution medium was maintained at 370C ±

20C. The agitation intensity was 50 rpm. The sampling time

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specified was modified instead of withdrawing a single sample at

10 min interval serial sampling was done. Equal volume of fresh

medium having same temperature was replaced at each time.

The samples were suitably diluted and the amount of active

ingredient was determined spectrophotometrically with respect

to the reported methods.

I. DISSOLUTION KINETICS (Higuchi WI, 1962)

Method used to compare dissolution data is:

Model Dependent Methods (zero order, first order, Higuchi

and Korsmeyer’s- Peppas).

Drug release kinetics

Drug release kinetics was studied from the datas obtained

from in-vitro drug release studies which were plotted in various

kinetics models: Zero order (equation 1) as Cumulative

percentage of drug released against Time, First order (equation

2) as Log cumulative percentage of drug unreleased against

Time, and Higuchi model (equation 3) as Cumulative percentage

of drug released against Square root of time.

C = K0 t (equation 1)

where K0 indicates zero order rate constant expressed

as concentration per time and t indicates the

time in hours.

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A graph of concentration against time gives a straight line

with a slope equal to K0 and intercept the origin of the axis.

log C = log C0 – K t/2.303 (equation 2)

where C0 be the initial concentration of drug,

K be the first order constant, and t is the time.

Q = K t1/2 (equation 3)

where K indicates the constant of the system, t indicates the

time in hours.

Drug release were plotted in Korsmeyer equation (equation

4) as Log cumulative percentage of drug released against Log

time, and the exponent was calculated from the slope of the

straight line.

Mt / Mα = K tn (equation 4)

where Mt / Mα is the fraction of solute release, t is the release

time, K is the kinetic constant

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11. Evaluation of Tablets