Comparative In-Vitro Evaluation of Marketed Paracetamol Tablets

 

T. Mamatha, Md. Raheem, S. Imam Pasha, Md. Zubair.

Sultan–Ul–Uloom College of Pharmacy, Road No.3, Banjarahills, Hyderabad-500034, (A.P.), India.

 

 

ABSTRACT

The aim of the present study is to investigate the physicochemical equivalence of five brands of tablets containing paracetamol purchased from different retail pharmacy outlets in Hyderabad, Andhrapradesh, India. The tablets were evaluated for uniformity of weight, friability, hardness, thickness, disintegration, dissolution and assay. All the five brands of the tablets passed the Indian Pharmacopoeia (IP) standards for all in vitro evaluation tests. There was no significant difference in the amount of paracetamol released from the different brands (P>0.05).  These results indicate that the tablets of paracetamol purchased from retail outlets in Hyderabad are manufactured and marketed from WHO GMP certified Indian companies. Further work is recommended on bioequivalence of these tablets.

 

KEYWORDS: Paracetamol, tablets, evaluation, marketed.

 

 

INTRODUCTION:

 

The increase in the number of generic drug products from multiple sources has placed people involved in the delivery of health care in a position of having to select one from among several seemingly equivalent products. For instance, in 1975 approximately 9% of all prescription drugs dispensed in the United States were generic versions1. This figure rose to 20% in 1984 and 40% in 1991. Over 80% of the approximately 10,000 prescription drugs available in 1990 were obtained from more than one source and variable clinical responses to these dosage forms supplied by two or more drug manufacturers is documented2. These variable responses may be due to formulation ingredients employed, methods of handling, packaging and storage and even the rigors of in-process quality control. Thus, there is need to determine their pharmaceutical and therapeutic equivalence in order to ensure interchangeability.

 

However, many developing countries do not have an effective means of monitoring the quality of generic drug products in the market. This results in widespread distribution of substandard and/or counterfeit drug products. It was in view of this fact that the World Health Organization issued guidelines for global standard and requirements for the registration, assessment, marketing, authorization and quality control of generic pharmaceutical products3. This was to give technical guidelines to national regulatory authorities such as NAFDAC (National Agency for Food, Drug, Administration and Control), which is responsible for drug administration and control, on the quality of drug dosage forms generally available in the market. Generic drug products must satisfy the same standards of quality, efficacy and safety as those applicable to the innovator products. Preliminary physicochemical assessment of the products is very important and in vitro dissolution testing can be a valuable predictor of the in vivo bioavailability and bioequivalence of oral solid dosage forms4.

 

 

Paracetamol has been in use as an analgesic for home medication for over 30 years and is accepted as a very effective treatment for the relief of pain and fever in adults and children.

 

It is used mainly for its pain relief properties either as a medicine prescribed by a doctor or it can be purchased as an over-the-counter medicine both in retail pharmacies or grocers shops. The recommended adult dose of paracetamol is two 500 mg tablets, with four hours between doses, and no more than eight tablets in 24 hours. Paracetamol is rapidly absorbed, the soluble form being absorbed faster than the solid tablet form. The peak blood level for both forms is similar and is usually less than 20 mg/litre following a 1000 mg dose. Peak serum levels usually occur 30 minutes to 2 hours after ingestion. Elimination from the body is rapid with a half-life of about two hours5.

 

Paracetamol is primarily metabolised by the liver. Most of it is combined with glucuronide and sulphate, which account for about 90% of the dose excreted. About 5% of the dose is excreted unchanged and a further 5% is oxidised to a benzoquinoneimine, which is then combined with glutathione and metabolised on to cysteine and mercapturate compounds which are safely excreted.

 

Paracetamol is a white, odourless crystalline powder with a bitter taste, soluble in 70 parts of water (1 in 20 boiling water), 7 parts of alcohol (95%), 13 parts of acetone, 40 parts of glycerol, 9 parts of propylene glycol, 50 parts of chloroform, or 10 parts of methyl alcohol. It is also soluble in solutions of alkali hydroxides. It is insoluble in benzene and ether. A saturated aqueous solution has a pH of about 6 and is stable (half-life over 20 years) but stability decreases in acid or alkaline conditions, the paracetamol being slowly broken down into acetic acid and p-aminophenol5.

 

MATERIALS:

Five brands of paracetamol tablets (A to E) were obtained from different retail outlets in Hyderabad, Andhrapradesh, India. Paracetamol drug was donated by Aurobindo pharmaceuticals (Hyderabad, India) and all other chemicals used were of analylitical grade.

 

METHODS:

Weight variation test:

20 tablets were selected randomly and weighed individually using digital balance (Sartorius). The average weight was calculated and individual weight was compared to the average weight. Calculated the percentage deviation. The tablets meet the requirement if not more than two tablets are out of percentage limits and no tablet differs from more than two times the percentage limit6. The same procedure was followed for all the five brands of paracetamol tablets.

 

Friability test:

20 tablets were selected randomly and weighed individually using digital balance (Sartorius, GE 212). The weighed tablets were placed in  friabilator (Roche friabilator). It consists of two chambers, revolves at a speed of 25 rpm. The tablets were placed in plastic chamber. The chamber is rotated for 4 minutes (100 revolutions).during each revolution the tablets fall from a height of 6 inches. The tablets were removed, dusted and reweighed. The tablets were considered to be of good quality if the loss in weight is 0.5-1% 6. The same procedure was followed for all the five brands of paracetamol tablets.

 

Disintegration test:

The disintegration test was performed by taking one tablet in each of the six tubes of the basket. The apparatus (Secor, India) was operated using distilled water as immersion fluid at 37 ± 2 o C for few minutes. The disintegration time was noted down. Repeated the same procedure for all brands of marketed paracetamol tablets. The tablets pass the test if all gets disintegrated. If 1 or 2 tablets fail to disintegrate, repeat the test on 12 additional tablets, not less than16 of the total 18 tablets should disintegrate completely6. Repeated the same procedure for all brands of marketed paracetamol tablets.

 

Dissolution Test:

Dissolution test was performed in  IP dissolution bath using apparatus I (paddle method) at 50 rpm. The apparatus (Electrolab, TDT-06P) was assembled and one tablet containing 500 mg of paracetamol was placed in 900 ml of phosphate buffer pH 5.8 which was warmed to 37 ± 0.5 o C previously. At 5, 10, 20 and 30 min, 5 ml of sample was withdrawn and replaced with fresh dissolution medium. The samples were filtered and diluted suitably with the buffer solution. The amount of paracetamol released was determined spectrophotometrically at 243 nm using phosphate buffer pH 5.8 as blank6. 

 

Thickness Test:

The thickness of ten tablets was measured using vernier calipers. The same method was followed for all brands of tablets.

 

Hardness Test:

The tablet hardness was measured by using Pfizer (Secor, India) hardness tester. Ten tablets were used from each brand.

 

Assay:

Weighed and powered 20 tablets. Weighed accurately a quantity of the powder containing about 0.15 gm of paracetamol, added 50 ml of 0.1 M NaOH, diluted with 100 ml of water. Shaken for 15 minutes and added sufficient water to produce 200 ml. Mixed, filtered and diluted 10 ml of filtrate to 100 ml with water. To 10 ml of resulting solution added 10 ml of 0.1 M NaOH, diluted to 100 ml with water and mixed. Measured the absorbance of resulting solution at the maximum at about 257 nm using UV visible spectrophotometer (Shimadzu Pharmspec1700, Shimadzu Inst. Japan). Calculated the content of paracetamol taking 715 as the specific absorbance at 257 nm.

 

RESULTS AND DISCUSSION:

The results of the physicochemical properties of the various brands of paracetamol are presented in Table 1. All brands showed acceptable uniformity of weight as none had percent deviation in weight  >5 % as stipulated by IP. The hardness of the tablets is an essential criterion in the determination of the ability of the tablets to resist chipping, abrasion or breakage under conditions of storage, transportation and handling before storage7. The hardness of the tablets is ranged from 9.04 ± 0. 23 to 13.90 ± 0.61 kg.

 

The friability, which is designed to evaluate the ability of the tablet to withstand abrasion during packaging, handling and shipping7. It was found to be in the range of  0.45 ± 0.018 to


Table 1. Physicochemical properties of five brands of paracetamol tablets*

Code of brand

Average weight (mg)

Friabilitya (%)

Hardness (kg)

Thickness (mm)

Disintegration timea (sec)

Assay (%)

% drug releaseda

A

598 ± 5.87

0.60 ± 0.021

12.68 ± 0.54

4.11 ± 0. 12

76 ± 5.98

97.34 ± 1.34

101.34 ± 2.87

B

631 ± 6.23

0.45 ± 0.018

9.04 ± 0. 23

4.32 ± 0.14

86 ± 3.72

98.37 ± 1.82

97.21 ± 3.81

C

575 ± 2.90

0.59 ± 0.023

11.64 ± 0.44

4.39 ± 0.08

110 ± 8.13

99.36 ± 2.11

96.23 ± 2.76

D

622 ± 4.72

0.79 ± 0.024

13.26 ± 0.51

4.13 ± 0.09

96 ± 4.86

96.75 ± 0.97

99.56 ± 1.87

E

 571 ± 9.04

0.75 ± 0.015

13.90 ± 0.61

4.03 ± 0.10

69 ± 2.03

96.71 ± 1.69

98.38 ± 2.41

* All values represent mean ± S.D, a  n=3

 

 

Figure 1. Drug release profile of five brands of paracetamol tablets (n=6)

 

0.79 ± 0.024. For compressed tablets, percentage loss in weight of less than 1 % is usually acceptable. The results showed that all brands were confirmed to the required standard for friability.

 

The disintegration time was found to be between 69 ± 2.03 and 110 ± 8.13 sec and was within pharmacopoeial limit. The disintegration test measures the time required for tablets to disintegrate into particles. This is necessary condition for dissolution and could be the rate determining step in the process of drug absorption.

 

The thickness was ranged from 4.03 ± 0.10 to 4.39 ± 0.08 mm and found to be uniform.

The percent purity of all brands was found to be within pharmacopoeial limit.

 

The dissolution test is a measure of the amount of the drug released into the dissolution medium with time. The percentage drug release with time was shown in figure 1.The total amount of paracetamol was released within 30 min in all brands. There was no significant difference in the amount of paracetamol released from the different brands (P>0.05). 

 

CONCLUSION:

All the five brands of paracetamol tablets passed in vitro evaluation tests to meet the requirement according to IP. Further work is recommended to know bioequivalence of these tablets.

 

 

ACKNOWLEDGEMENTS:

The authors are grateful to the management of the institute, Sultan-Ul-Uloom Educational Society, Banjarahills, Hyderabad for providing the facilities. The gift sample of Paracetamol by Aurobindo Pharmaceuticals, Hyderabad, India is highly acknowledged.

 

REFERENCES:

1.       Covington TR. Generic drug utilisation: Overview and guidelines for prudent use. Clin Research Reg Affairs. 1992; 9: 103-26.

2.       Shah HK. Generics capture new prescription markets. Perspectives in Pharmacy Economics 1992; 4: 3.

3.       World Health Organization Expert Committee on specifications for Pharmaceutical Preparations. 34th Report WHO Technical Report Series, No. 863, Geneva, Switzerland: WHO 1996; 114-54

4.       Itiola OA, Pilpel N. Effects of interacting variables on the disintegration and dissolution of metronidazole tablets. Pharmazie. 1996; 51: 987-9

5.       http://www.pharmweb.net/pwmirror/pwy/paracetamol/pharmwebpic.html

6.       Indian Pharmacopoeia. Vol. III, New Delhi, Indian Pharmacopoeia Commission. 2007; 516-1517.

7.       Leon Lachman and Herbert A Liberman. The theory and practice of industrial pharmacy. Bombay, 1987; Third edition:  293-345

 

 

 

Received on 14.05.2009

Accepted on 16.07.2009     

© A&V Publication all right reserved

Research Journal of Pharmaceutical Dosage Forms and Technology. 1(2): Sept.-Oct. 2009, 100-102