Chapter 7 Evaluation 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. b. c. d. e. f.
g. A.

Thickness and diameter Weight variation Hardness Friability Drug content Disintegration time In- vitro dissolution and its Kinetics studies 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 manufacturers 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.

54

Chapter 7 Evaluation of Paracetamol Tablets

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

Average weight - Individual Average weight

weight

X 100

55

Chapter 7 Evaluation of Paracetamol Tablets

Average Weight 130 mg or less More than 130 mg through 324 mg More than 324 mg Percentage Difference 10 7.5 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,

56

Chapter 7 Evaluation of Paracetamol Tablets

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
57

Chapter 7 Evaluation of Paracetamol Tablets

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)

58

Chapter 7 Evaluation of Paracetamol Tablets

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
59

Chapter 7 Evaluation of Paracetamol Tablets

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 Korsmeyers- 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 where as time in (equation 1)

K0 indicates zero order rate constant expressed concentration per time and t indicates the hours.
60

Chapter 7 Evaluation of Paracetamol Tablets

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 where C0 be the initial concentration of drug, K be the first order constant, and t is the time. Q = K t1/2 where (equation 3) (equation 2)

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 straight line. Mt / M = K tn where (equation 4) the slope of the

Mt / M is the fraction of solute release, t is the release time, K is the kinetic constant

61