COMPARATIVE EVALUATION OF DIFFERENT PARACETAMOL BRANDS

THE PARACETAMOL TABLETS IS COMMONLY TAKEN AND PRESCRIBED FOR FEVER , SO HERE WE HAVE MADE PRACTICAL IS IT TRUE EVALUATION LABEL AND WHICH BRAND IS MORE SAFE.

1. POST MARKET IN VITRO COMPARATIVE EVALUATION OF DIFFERENT BRANDS OF PARACETAMOL TABLETS.

2. The term quality control refers to sum of all procedures under taken to ensure the identity purity of a particular pharmaceutical product. Such proceduers may range from the performance of simple chemical experiments which determine the identity and screening for the presence of particular pharmaceutical substance to more complicated requirements of pharmacopoeial monographs . The quality of a product may deviate from the standard required so carrying out analysis is important in order to determine the quality. Testing a pharmaceutical product involves chemical, physical and some time microbiological evaluation or test. Introduction

3. Genearl Appearance: Size , Thickness, diameter, Shape, Colour , Surface texture Determination of Weight variation Determination of Hardness Determination of Friability Determination of Disintegration Determination of Pharmacopoeial assay Determination of Dissolution Quality Control tests for tablets

4. Paracetamol is virtually the sole survivor of the so-called “aniline derivatives” or “aniline analgesics”: acetanilide, phenacetin and paracetamol (acetaminophen). Phenacetin and paracetamol are both derivatives of acetanilide . Acetanilide was serendipitously found to possess antipyretic activity and quickly introduced into medical practice under the name of antifebrin, and was shown to possess both analgesic and antipyretic activities. But its unacceptable toxic effects, the most alarming being cyanosis due to methemoglobinemia , prompted the search of less toxic aniline derivatives. A number of compounds were tested and phenacetin ( acetophenetidin ) and N-acetyl-p-aminophenol ( paracetamol ) were found to be the most successful. Paracetamol had been synthesized by Morse in 1878 and was first used in medicine by von Mering in 1893. Paracetamol

5. Chemistry of Paracetamol Paracetamol is a 4-hydroxy acetanilide. 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-aminophenol.

6. The study aim to analyze the different brands of paracetamol 500mg tablets for its quality by performing weight variation , Hardness, friability, disintegration, pharmacopoeial assay and dissolution test. Aim and objective

7. Literature survey. Procurement of different brands of paracetamol from market. Evaluation Parameters General appearance : Size, Thickness, Diameter, Shape, Colour, Odour, Surface texture Weight variation Hardness Friability Disintegration Pharmacopoeial assay Dissolution Plan of work

8. Experimental , Results & Discussion

9. The parameter like shape, colour, odour, and surface texture were studied by visual identification while thickness and diameter was measured using vernier calliper. Sample Thickness (mm) Diameter (mm) Shape Colour Odour Surface texture A 4 12 Rounded White Odourless Smooth B 4 13 Rounded White Odourless Smooth C 4 13 Rounded White Odourless Smooth D 5 13 Rounded White Odourless Smooth Evaluation of tablets General Appearance:

10. All the four brands of paracetamol (500 mg) showed a percentage weight variation within the range of ±5 and, therefore, comply with the specification of USP.   Sr. no. Weight of individual tablets( gm ) A B C D 1. 0.993 0.929 0.943 0.888 2. 0.998 0.930 0.946 0.876 3. 0.987 0.931 0.945 0.869 4. 0.969 0.929 0.951 0.915 5. 0.990 0.930 0.961 0.908 6. 0.988 0.925 0.958 0.885 7. 0.972 0.926 0.958 0.880 8. 0.993 0.929 0.959 0.865 9. 0.982 0.929 0.937 0.879 10. 0.991 0.929 0.962 0.891 11. 0.988 0.931 0.956 0.867 12. 0.990 0.928 0.947 0.863 13. 0.990 0.933 0.943 0.851 14. 0.973 0.930 0.942 0.830 15. 0.990 0.929 0.932 0.855 16. 0.999 0.929 0.963 0.911 17. 0.942 0.927 0.962 0.870 18. 0.991 0.932 0.972 0.931 19. 0.977 0.925 0.942 0.918 20. 0.990 0.915 0.938 0.884 Mean±SD 0.984±0.012 0.928±0.003 0.950±0.010 0.881±0.025 Weight Variation Test Weight variation data of various brands of paracetamol

11. Hardness Test Sample Hardness(kg/cm 2 ) A 4 B 5 C 7 D 4.2 In the study, it was found all the brands of paracetamol passed the test of tablet crushing strength or hardness and have acceptable crushing strength of between 4 kg/cm 2 to 10 kg/cm 2 . Hardness data of Paracetamol brands Comparative study of Hardness testing of all paracetamol brands

12. Sample Initial Weight ( gm ) Final Weight ( gm ) W b -W a ( gm ) %Friability A 4.977 4.949 0.028 0.5625 B 4.640 4.622 0.018 0.38 C 4.751 4.741 0.01 0.210 D 4.415 4.401 0.014 0.3171 All the four brands of paracetamol have passed the friability test and have meet the specification of USP which specifies that the friability study must not lose 1% of their initial weight. Friability testing Friability data of Paracetamol brands Comparative study of Friability testing of all paracetamol brands

13. Sample Time required to disintegrate ( min.sec ) A 23 B 28.44 C 25.20 D 26 All the four brand of Paracetamol have a disintegration time that is within the acceptable range and have met the specification of USP where a majority of the tablets have a maximum disintegration time was found to be within 30 minutes. Disintegration Test Disintegration time of Paracetamol brands Comparative study of disintegration time of all paracetamol brands

14. Sample % Drug Content A 98.15 B 99.34 C 96.78 D 98.01 Test for percentage of content is based on the assay of the individual content of active ingredient of a number of single dose units. The IP, USP and BP specifications for assay are that the paracetamol contents should not be less then 90 and not more then 110. Pharmacopoeial Assay % Assay of Paracetamol brands Comparative study of % assay of all paracetamol brands

15. Dissolution test was done by using test U.S.P. Type- 1 (Basket) Single flask Dissolution Apparatus. Gastric Fluid was taken as a Dissolution Medium. The % drug release of each brand of paracetamol tablet was calculated by using standard calibration curve method. Sr.no Concentration ( µg/ml) Absorbance 1.  5 0.232 2. 10 0.358 3. 15 0.567 4.   20 0.723 5.   25 0.884 6.   30 1.034 Dissolution Test Calibration data of standard paracetamol Calibration curve of standard paracetamol

16. Sr.No . Time (min) A B C D Abs. %drug release Abs. %drug release Abs. %drug release Abs. %drug release 1. 15 0.978 51.64 0.964 50.94 1.027 54.55 1.347 72.9 2. 3. 1.399 75.47 1.297 69.66 1.355 72.9 1.566 85.14 3. 45 1.672 90.72 1.530 82.8 1.648 89.46 1.695 92.52 4. 60 1.774 96.84 1.829 99.54 1.799 97.92 1.771 96.66 Thorough evaluation, highest percent release concentration was found in Sample B, ( 99.54 %) while the lowest percent release concentration was recorded in sample D (96.66%).The result complies with the requirement of USP which states at least 80% of drugs should be released within 30 minutes. Percetage drug release data of paracetamol brands Comparative study of % drug release of all paracetamol brands

17. Summary

18. Branded products of paracetamol is collected from market and various test on various parameters were performed by using suitable quality control tests like appearance, weight variation, hardness, friability, drug content, disintegration and dissolution indicate that values were within permissible limit for all tablets. Tablets are required to meet a weight variation test as the active ingredient comprises a major portion of the tablet and control of weight may be presumed to be an adequate control of drug content uniformity . 20 tablets were taken and weighed ,their average weight was calculated. All the four brands of paracetamol (500 mg) showed a percentage weight variation within the range of ±5 and, therefore, comply with the specification of USP. Tablets require a certain amount of strength, or hardness to withstand the mechanical shocks of handling and transportation yet soft enough to be able to disintegrate properly after swallowing. Since there is also a relationship between hardness and disintegration rate of the tablets, it is essential that the hardness of the tablets are within the acceptable range. Tablets with increased hardness values tend to have increasing disintegration time . Hardness test was done by using Monsanto hardness tester . T he study showed all brands of paracetamol group passed the test of tablet crushing strength or hardness and have acceptable crushing strength of between 4 kg/cm 2 to 10 kg/cm 2 . Summary

19. The friability test was performed by using Roche friabilator with 5 tablets of each brand of paracetamol tablet . All the four brands of paracetamol have passed the friability test and have meet the specification of USP. Disintegration is essential for better bioavailability which results in better absorption and consequently better therapeutic action. The effectiveness of a drug is related to its disintegration time . The time taken for disintegration of tablet was recorded . All the four brand of Paracetamol have a disintegration time that is within the acceptable range and have met the specification of USP where a majority of the tablets have a maximum disintegration time was found to be within 30 minutes. Dissolution profile of four brands was performed, to provide information regarding biological bioavailability and brand to brand consistency. A dissolution test was intended to determine the percent release of the samples in 60 minutes . Assay is a test carried out for the purpose of estimating the potency of material In this study the assay was performed on different brands of paracetamol tablet in compliance to IP to asses % content of paracetamol . IP specific the content of paracetamol to be between 95-105% of stated amount. The result for assay of paracetamol .

20. Conclusion & Future scope

21. Paracetamol is a well established and proven analgesic and antipyretic drug. Therapeutic response of any formulation depends on its quality parameter . From the study it was identified that all the quality control tests like weight variations, hardness, friability, pharmacopoeial assay , disintegration , dissolution of all paracetamol brands complied the specification while Variations were obtained in hardness of tablets. Further studies could also include the HPLC method for routine analysis of paracetamol in bulk as well as in pharmaceutical dosage formulation.

22. Reference: Mosharraf Zinia . Determination of the quality control parameters of Paracetamol Tablets in Bangladesh Pharma Market: 03-09. D.R.Jadge ., A.N.Deshpande ., A.B.Gadgul ., Y.A.Pandilwar ., O.P.Patil . Comparative In-vitro evaluation of Different Brands of Paracetamol Tablets Marketed in Maharashtra State: International Journal of Pharmaceutical Science and Health care; 4(4): 40-42. Khan Imran., Baig Aliza., Rahman Zia- ur . Post-Marketed In-vitro comparative Evaluation of quality control parameters of Paracetamol Compressed Tablets manufactured in Local Industrial Zones of kpk Pakistan: THE PHARMA INNOVATION-JOURNAL: 2(3): 11-5. S. S. dahiwal ., S. G. Bhokare . In-vitro Evaluation of marketed brands of paracetamol Tablets in India using quality control tests: IJPPR; 10(1):182-192. Revankar shreenivas , Pharmaceutical evaluation and comparision of various brands of paracetamol tablet formulation: International Journal of Pharma and Bio science; 4(4): 96-101. Karmakar Palash ., Kibria Golam.In -vitro comparative evaluation of quality control parameters between paracetamol and paracetamol /caffeine tablets available in Bangladesh: Karamkar and Kubria , International Current Pharmaceutical Journal 2012; 1(5): 103-109.