EXPERIMENT NO :- 1 MONOGRAPH OF ASPIRIN POWDER IP96

AIM:- To perform defferent test listed under the monograph of aspirin including assy as per IP-1996. REFERENCE:1) Indian pharmacopoeia vol-1& 2, Government of India; ministry of health and family welfare; controller of publications; Delhi-1996 page no: 69,A-43,A-45,A-78,A-90.
2) Beckett A.H, stenlake J.B practical pharmaceutical chemistry; part-1;

CBS publishers; New Delhi; 4th edition; 1999 Page no:147,149. APPRATUS: Burette, Pipette, conical flask, iodine flask, volumetric flask, nesslers cylinder, measuring cylinder, beaker, weight box, glass rod.. REAGENTS & CHEMICALS:sodium hydroxide, dilute sulphuric acid, ferric chloride solution, 5%w/v sodium carbonate, ethanol (95%), acidic ferric ammonium sulphate solution, 0.01%w/v solution of salicylic acid, 0.5M sodium hydroxide. 0.5M hydrochloric acid, Phenol red, 0.75g Anhydrous sodium carbonate, Methyl red, Barium chloride, PRINCIPLE:- 1) Acid-base titration 2) Back titration. THEORY:Acetyle salicylic acid under goes hydrolysis when treated with worm solution of sodium hydroxide producing sodium ethanoate to following reaction.

An excess of sodium hydroxide is used, the unreacted alkali may be determined by back titration with standard hydrochloric acid. Aspirin is liable to be contaminated with salicylic acid which may be present as aresult of incomplete conversion to aspirin during manufacture or through hydrolysis on storage. Hydrolysis also release acetic acid which can often be detected in samples of aspirin by odour. The quality of aspirin is there fore, conrolled by a combination of double assay procedure and a separate colorimetric limit test for salicylic acid based on the reaction of its free phenolic group with iron () chloride. IN the assay the sample is dissolved in ethanol (95%) because of its low solubility in water (1 in 300) & tirrated directly with sodium hydroxide using phenolphthalein as indicator . Aspirin & contaminating acedtic acid & salicylic acids are tirrated in this procedure. However for calculation purposes in determining compliance with the standard, it is assumed that all material titrated is aspirin. Aspirin alone is determined by refluxing the neutralized sample solution with excess standard sodium hydroxide to hydrolyse the acetoxy group, cooling & back titrating the excess acid with standard acid. The difference between the volume of standar sodium hydroxide solution consumed in the first and second tirration is a measure of the salicylic acid & acetic acid contamination of the product and must not be more than 0.4 ml for each 0.5 g of sample, equlivalent to (1.45%). STANDARDIZATION OF HYDROCHLORIC ACID:Titration of strong bases with strong acids gives salts which are not hydrolysed in aqueous solution and the solution is therefore neutral. The pH changes in the region of equivalence point are sufficiently large to permit a wide choice of indicator. Methyl orange is usually used. REACTIONS:-

Procedure: 1) Standardization of 0.5M Hydrochloric acid:Weigh accurately anhydrous sodium carbonate 0.75g. Dissolve in some water and titrate with prepared hydrochloric acid by using methyl red as indicator. 2) Assay of Aspirin:Weigh accurately about 1.5g. Dissolve in 15ml of ethanol, add 50ml of 0.5M sodium hydroxide. Boil gently for 10 mins, cool and titrate excess of alkali with 0.5M hydrochloric acid using phenol red solution as indicator. Repeat the operation without substance being examined. The difference between the titration represents amount of sodium hydroxide required. 3) Preparation of reagents:a) 0.5M sodium hydroxide Dissolve 21g of sodium hydroxide pellets in water. Make up volume to 1000 ml using water. b) 0.5M Hydrochloric acid:Take 42.5 ml of concentrated hydrochloric acid and make upto 1000ml using water. Factor:- Each ml of 0.5M sodium hydroxide 0.04504g of aspirin. Each ml of 1M Hydrochloric acid 0.2764g of sodium carbonate. 4: Identification Tests:B) Boil about 0.5g with 10 ml of sodium hydroxide solution for 3 min. Crystalline precipitate is produced and the odour of acetic acid is perceptible. Filter and dissolve the precipitate in about 2ml of water and add ferric chloride test solution. A deep violet color is produced. C) To the filter obtained in test B, add 3ml of ethanol and 3 ml of sulphuric acid and warm. The odour of ethyl acetate is perceptible. D) Melts at about 1420C. E) Clarity and color of solution in ethanol:- A 1 % w/v solution in ethanol (95%) is clear and not more intensely colored than reference solution BS8.

F) Clarity of solution in alkali:- A 5% w/v solution in 5% w/v solution of sodium carbonate is clear. G) Chloride Test:- Boil 1.75g with 75 ml of water for 5 min, cool and add sufficient water to restore the original volume and filter. 25ml of filtrate complies with limit test for chlorides. Limit Test for Chloride:Dissolve the specified quantity of substance being examined in water or prepare a solution as directed in the individual monograph. Transfer to the Nessler cylinder. Add 10 ml of dilute nitric acid, except when nitric acid is used in preparation of the solution, dilute to some with water and add 1 ml of 0.1M silver nitrate. Stir immediately with a glass rod and allow to stand for 5 min. Protect from light. Opalascence produced is not more intense than that obtained by treating a mixture of 10 ml of chloride standard solution and 5 ml of water in same manner. H) Sulphate test:10 ml of filtrate obtained in the test for chloride complies with the limit test of sulphate. Limit Test of Sulphate:The solution used for this test should be prepared with distilled water. 1ml of 25%w/v of solution of barium chloride in Nessler Cylinder and add 1.5ml of ethanolic sulphate standard solution (10ppm), mix and allow to stand for 1 min. Add 15 ml of solution prepared as directed in individual monograph or a solution of specified quantity of substance being examined in 15 ml of water and 0.15 ml of 5M acetic acid. Add sufficient water to produce 50 ml. Stir immediately with glass rod and allow to stand for 5 min. When viewed transversely against a black background any opalescence produced is not more intense than that obtained by treating in same manner 15 ml of sulphate standard solution(10ppm) in place of solution being examined. I) Test for salicylic acid:Dissolve 2.5 g in sufficient ethanol (95%) to produce 25 ml. To each of two matched Nessler cylinder add 48 ml water and 1 ml of a freshly prepared acid ferric ammonium sulphate solution. Into one cylinder pipette 1ml of freshly prepared 0.01% w/v solution of salicylic acid and into the other, 1 ml of test solution. Mix contents of cylinder. After 30

sec, the color in cylinder containing test solution is not more intense than that in cylinder containing standard solution Preparation of Acid Ferric Ammonium sulphate solution:Dissolve 0.2g of ferric ammonium sulphate in 50 ml of water. Add 6 ml of dilute nitric acid and add sufficient water to produce 100 ml. RESULT:-1) Molarity of prepared 0.5 M hydrochloric acid was found to be hydrochloric acid. 2) The percentage purity of given aspirin powder was found to be of aspirin. (I.P limit-99.5-100.5%w/w)