Chapter 7 Evaluation of Paracetamol Tablets EVALUATION OF PARACETAMOL TABLETS Almost
all all
Phar Ph arm maco acopoei oeias
includ clude e
som some
suiitabl su able
stan standa dard rds s and and test tests s to ensu ensure re the the qual qualit ity y of tabl tablet ets. s. The 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 ti time
g.
dissolution and its Kinetics studies In- vitro dissolution
A.
THICKNESS AND DIAMETER (Lachman et al., 1990) The The thic thickn knes ess s of indi indivi vidu dual al tabl tablet ets s is meas measur ured ed with with a
micr microm omet eter er,, whic which h give gives s us info inform rmat atio ion n abou aboutt the the vari variat atio ion n betw betwee een n tabl tablet ets. s. Tabl Tablet et thic thickn knes ess s sh shou ould ld be with within in a ±5 ±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.
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
55
weight
X 100
Chapter 7 Evaluation of Paracetamol Tablets Average Weight
Percentage Difference
130 mg or less
10
More than 130 mg through 324 mg
7.5
More than 324 mg
C.
5
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 dissolution release profiles as a function of the compressive force employed. Tablet hardness is the force necessary to break the tablet tablet diametri diametricall cally. y. Hardness Hardness is sometim sometimes es termed termed the tablet 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 diss dissol olut utio ion n sp spec ecif ific icat atio ion, n, if its its too too soft soft,, it cann cannot ot with withst stan and d hand handli ling ng when when deal dealin ing g with with proc proces esse ses s su such ch as coat coatin ing g or packag packagin ing g and shi shippi pping ng operat operatio ions. ns. The force force with with which 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 tab tablets. ets. Oral tabl ablets ets have ave a hard ardness ness of 4 to 10kg 0kg ; but 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. Pfzi fzier har hardnes dness s
test tester er was used for measur asuriing
the 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 The norm normal al revo revolu luti tion on of this this fria friabi bila lato torr is 25 25rp rpm. m. The The friability 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 friability It
is
expressed
in
percentage.
For
conventionally
comp compre ress ssed ed tabl tablet ets, s, the the limi limitt is 0.5% 0.5% to 1% of thei theirr weig weight ht,, chewab chewable le tablet tablet have have high high friabi friabili lity ty values values.. When When cappi capping ng 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 inso insolu lubl ble e coat coatin ing g of tabl tablet ets s or of caps capsul ule e sh shel ell, l, or of any any melted fatty substance from pessary or suppository suppository.. The The frag fragme ment ntat atio ion n of a tabl tablet et into into smal smalll frag fragme ment nts s 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 28-32 cycles cycles/m /min in throug through h a dista distance nce of 50-60m 50-60mm. m. Place Place 6 tablets in apparatus (i.e., in tubes of basket), add disc to each tube and operate the apparatus. apparatus. At the end of the 15min 15min all the tabl tablet ets s sh shou ould ld disi disint nteg egra rate te,, comp comple lete tely ly with withou outt leav leavin ing g any any resid residue ue in the basket basket.. Where Where as for other coated coated tablet tablets s the disintegration disintegration time will vary accordingly. G.
DRUG CONTENT (IP, 2007)
58
Chapter 7 Evaluation of Paracetamol Tablets 20 tabl tablet ets s were were weig weighe hed d and and powd powder ered ed.. A quan quanti tity ty 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 Dissolution was carried out using USP dissolution dissolution apparatus II (Rotating paddle apparatus). Dissolution of tablets was carried out in 900 ml dissolution medium. The dissolution medium for Para aracetamol
tablet
was
phosphate
buffer
pH
5.8.
The
temperature of the dissolution medium was maintained at 370C ± 20C. The The agit agitat atio ion n inte intens nsit ity y was was 50 rpm. rpm. The The samp sampli ling ng time 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 The sampl samples es were were sui suitab tably ly dilut diluted ed and the amoun amountt of active active ingredient was determined spectrophotometrically with respect to the reported methods. I.
DISSOLUTION KINETICS (Higuchi WI, 1962) Method used to compare dissolution data is: •
Mode Modell Depe Depend nden entt Meth Method ods s (zer (zero o orde order, r, firs firstt orde order, r, Higuchi and Korsmeyer’sKorsmeyer’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 kin kineti etics
model odels: s:
Zero ero
order der
(equ (equat atiion
1)
as
Cum Cumulat ulatiive
percentage of drug released against Time, First order (equation 2) as Log cumula cumulativ tive e percen percentag tage e of drug drug unrele unrelease ased d agains againstt Time, and Higuchi model (equation 3) as Cumulative percentage of drug released against Square root of time. C = K 0 t where as time in
(equation 1)
K 0 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 K 0 and intercept the origin of the axis. log C = log C0 – K t/2.303 where
(equation 2)
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)
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, time, and the exponen exponentt was calcula calculated ted from from
the slope slope of the
straight line. Mt / Mα = K tn where
(equation 4)
Mt / Mα is the fraction of solute release, t is the release time, K is the kinetic kinetic constant
61
