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Method of Analysis for Cross Povidone

Know the procedure of analysis of Cross Povidone as a raw material in pharmaceutical quality control laboratory.
1. Description
A white to creamy-white, hygroscopic powder having a faint odor.

2. Solubility
Insoluble in water and in ordinary organic solvents (1 mg in 10 ml)

3. Identification
A. The IR absorption spectrum of the sample should be concordant with the reference spectrum obtained with the Cross Povidone WRS.
B. Color test
Reagent required
0.1N Iodine solution
Starch test solution
Weigh accurately about 1.0 gm of the sample and suspend it into 10 ml of water. To this add 0.1 ml of 0.1N Iodine, and shake for 30 seconds. Add 1.0 ml of starch TS, and shake.
No blue color develops.

4. pH
Limit: Between 5.0 and 8.0
Weigh accurately 250 mg of sample and dissolve in 25 ml of water. Shake for 15 minutes. Measure the pH of resulting solution.

5. Water
Limit: Not more than 5.0 %
Reagent required
Anhydrous methanol AR
KF reagent
Transfer 35 to 40 ml of methanol to the titration vessel, and titrate with K.F. reagent, standardized earlier, to the electrometric end point to consume any moisture that may be present. Quickly and accurately add 250 mg substance, mix, and again titrate with the reagent to the electrometric end point. Calculate the % of water using formula.

                                   V x F x 100
Water (% w/w) = ----------------
V = Volume of K.F. reagent consumed (ml)
F = Water equivalence factor of reagent in mg/ml
A = Weight of substance in mg

6. Residue on ignition
Limit: Not more than 0.4 %
Reagent required     
Sulphuric acid AR
Heat a silica crucible to redness for 10 min., allow cooling in a desiccator and weighing. Place about 2 g of accurately weighed substance being examined in the silica crucible and ignite at about 800° C, cool, weigh and again, ignite for 15 min. and repeat this procedure until two successive weighing do not differ by more than 0.5 mg.

                                            W3– W1
% Residue on ignition = -------------- x 100
                                            W2 – W1
W1 = Weight of empty platinum crucible.
W2 = Weight of crucible + sample.
W3 = Weight of crucible + residue.  (After ignition)

7. Water-soluble substances
Limit: The weight of the residue does not exceed 75 mg (1.5%).
Weigh 25.0 gm of the sample into a 500-ml beaker. To this add 200 ml of water and stir on a magnetic stirrer for 1 hour. Transfer the resulting suspension into a 250-ml volumetric flask with the aid of 25 ml of water. Dilute to 250 ml with water and mix. Allow it to stand for some time so that the solid particles settle down. Filter about 100 ml of the supernatant liquid through a 0.45-mm membrane filter, protected against clogging by superimposing a 3-mm membrane filter. While filtering, stir the solution above the filter manually or by means of a mechanical stirrer and taking care not to damage the filter physically. Transfer about 50 ml of the filtrate to a tared 100-ml beaker, evaporate to dryness, and dry at 110°C for 3 hours.
The weight of the residue does not exceed 75 mg (1.5%)

8. Heavy Metals
Limit: Not more than 0.001%
Reagent required
Lead standard solution (2ppm.Pb.)
Hydrochloric acid AR.
Dilute ammonia solution
Dilute acetic acid solution
Hydrogen sulfide solution
Standard solution: Pipette 5 ml of lead standard solution (2 ppm Pb) and transfer to 50 ml Nessler cylinder. Dilute to 25 ml with water. Adjust the pH of the solution between 3.0 and 4.0 with dilute acetic acid or dilute ammonia solution, Make up the volume upto about 35 ml with water and mix.
Sample solution: Moisten the residue obtained in the test for sulphated ash with few drops of Hydrochloric acid and evaporate almost to dryness on a water bath.  Dissolve the residue in 10 ml of water by warming, cool and transfer it to a test tube with the aid of 10 ml of water and 2 ml of dilute acetic acid. Dilute above solution to 25 ml with water. Transfer this solution into a 50 ml Nessler cylinder. Adjust pH between 3.0 and 4.0 with dilute acetic acid or dilute ammonia solution, dilute with water to about 35 ml and mix.
To each of the cylinders containing the standard solution and sample solution respectively, add 10 ml of freshly prepared hydrogen sulphide solution, mix, dilute to 50 ml allow standing for 5 minutes and viewing downwards over a white surface.
The color produced with the sample preparation is not more intense than that of standard preparation.

9. Vinylpyrrol idinone
Limit:  NMT 0.72 ml of 0.1N Iodine solution is consumed, corresponding to NMT 0.1 % of Vinylpyrrolidinone.
Reagent required
0.1N Iodine solution
0.1N Sodium thiosulphate solution
Starch test solution
Weigh accurately about 4.0 gm of the sample and suspend it into 30 ml of water. Stir for 15 minutes, centrifuge the suspension and filter the slightly turbid upper layer through the sintered-glass, 10-mm filter. Again stir the lower layer with 50 ml of water and filter similarly. Add 0.5 gm of sodium acetate to the combined filtrates and titrate with 0.1N Iodine solution, until the color of Iodine no longer fades. Then add 3.0 ml of 0.1N Iodine solution and allow it to stand for 10 minutes and titrate the excess iodine with 0.1N Sodium thiosulphate solution, adding 3 ml of starch test solution as the end point is approached. Perform a blank determination by omitting the sample and adjusting the pH of the solution as that of the sample solution, using acetic acid and then perform the titration.

10. Nitrogen content
Limit: Not less than 11.0 % and not more than 12.8 % of nitrogen, calculated on the anhydrous basis.
Reagent required
Potassium sulphate
Cupric sulphate
Titanium dioxide
Sulphuric acid
Sodium hydroxide (40%)
Boric acid solution (4%)
Methyl red – methylene blue TS
0.01N Sulphuric acid
Weigh accurately about 100 mg of the sample and transfer it into the digestion flask of the semi-micro Kjeldahl apparatus. To this add 5.0 gm of a powdered mixture of potassium sulphate, cupric sulphate and titanium dioxide (33:1:1). Wash down any adhering material from the neck of the flask with a fine jet of water. Add 7 ml of sulphuric acid by rinsing the wall and then swirl the flask. Heat the flask over a free flame until a clear, light green solution is obtained and further heat for 45 minutes. Cautiously add to the digestion mixture, 70 ml of water, cool the solution, and arrange for steam distillation. Add through a funnel, 30 ml of 40% sodium hydroxide solution in such a manner that the solution flows down the inner side of the flask and forms a layer below the acid layer. Rinse the funnel with 10 ml of water and close the apparatus tightly. Begin the distillation with steam immediately. Collect the distillate into a flask containing 15 ml of 4% boric acid solution to which 3 drops of methyl red - methylene blue TS and sufficient water to cover the end of the condensing tube have been added. Continue the distillation till the distillate measures to 80 – 100 ml. Remove the absorption flask, rinse the end of the condensing tube with a small quantity of water, and titrate the distillate with 0.01N sulphuric acid solution until a green color is obtained. Perform a blank determination, omitting the sample. Each ml of 0.01N sulphuric acid is equivalent to 140.1 mg of Nitrogen.
                   Net B.R. = Blank B.R. – Sample B.R.
B.R. = burette reading.

                                                                Net B.R. x F x N x   100                            
% Content of Nitrogen “as is” = ----------------------------------
                                                                           0.01x W
W= Weight of sample (in mg)
N= Normality of H2SO4 
F= Factor

                                                                                  % Content “as is” x 100
% Content of Nitrogen “On Dried” basis   = ---------------------------------
                                                                                         (100 – %Water)

Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of Pharmaceutical Guidelines, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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