Method of Analysis for Sodium Starch Glycolate : Pharmaceutical Guidelines

Method of Analysis for Sodium Starch Glycolate

Procedure for analysis of Sodium Starch Glycolate in pharmaceutical quality control laboratory.

1. Description
Very fine, white or off-white, free flowing odorless or almost odorless, very hygroscopic powder.

2. Solubility
Practically insoluble in water and gives a translucent suspension. Insoluble in most of the organic solvents.

3. Identification
A. The IR absorption spectrum of sample is concordant with the reference spectrum or with the spectrum obtained from sodium starch glycolate WRS.
B. Color reaction
Reagent required
0.005M Iodine
Procedure
Dissolve 2 g sample and disperse in 100 ml of water. Take 5 ml of above dispersion and add 0.05 ml 0.005M iodine. A dark blue color is produced.
C. Reactions of sodium salts (A)
Reagent required
15 % w/v solution of potassium carbonate
Potassium antimonate solution
Procedure
Take 2 ml of the solution obtained in the test for “Heavy metal”, add 2 ml of 15 % w/v solution of potassium carbonate and heat to boiling. No precipitate is produced. Add 4 ml of a freshly prepared potassium antimonate solution and heat to boiling. Allow to cool in ice and if necessary scratch the inside of the test-tube with a glass-red. A dense white precipitate is formed.
Reactions (B)
Reagent required
1M Acetic Acid
Magnesium Uranyl acetate solution
Procedure
Take 10 ml of the solution obtained in the test for “Heavy metal”, acidify the solution with 1 M acetic acid and add a large excess of magnesium Uranyl acetate solution, a yellow crystalline precipitate is formed.
D. Physical characteristics
Procedure
Take 4 g of the sample in a 250 ml stoppered measuring cylinder and add 20 ml of water. Shake well. To this gel, add 100 ml of carbon dioxide free water and shake well. A suspension forms that settles after standing.

4. pH
Limit: Between 5.5 and 7.5
Procedure
Take 2 g of the sample in a clean beaker and disperse it in 100 ml of Carbon dioxide free water. Measure the pH of the solution.

5. Heavy metals
Limit: Not more than 20 ppm
Reagent required
Lead standard solution (20 ppm Pb)
Dilute acetic acid
Dilute ammonia solution
50%v/v sulphuric acid
1M sulphuric acid
2M ammonium carbonate
Hydrochloric acid
Hydrogen Sulphide solution
Standard preparation: Pipette 1 ml of lead standard solution (20 ppm Pb) into a 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 up to 35 ml with water and mix.
Sample preparation: Take 4.0 g. of the sample in a silica crucible; add 2.0 ml of 50 % w/v of solution of sulphuric acid heat in a water bath and then cautiously over a flame at about 600°C. Continue heating until all black particles disappear, allow to cool, add 0.1 ml of 1M Sulphuric acid, heat to ignition once again and allow to cool. Add 0.1 ml of 2M ammonium carbonate, evaporate to dryness and cautiously ignite. To the residue, add 5 ml of HCl evaporate to dryness on the water bath and dissolved the residue in 100 ml of water. Transfer 25 ml of this solution to a Nessler cylinder, adjust the pH of the solution between 3.0 and 4.0 with dilute acetic acid or dilute ammonia solution. Make up the volume to 35 ml with water and mix.
Procedure
To each of the cylinders containing the standard preparation and sample preparation respectively, add 10 ml of freshly prepared hydrogen sulfide solution, mix, dilute to 50 ml, allow standing for 5 minutes and viewing downwards over a white surface. The color produced with sample preparation is not more intense than that produced with the standard preparation.

6. Iron
Limit: Not more than 20 ppm
Reagent required
20% w/v citric acid solution (Iron free)
0.05M sulphuric acid
Thioglycolic acid
Ammonia solution (Iron free)
Iron standard solution (20 ppm Fe)
Sample preparation: Take 50 ml of the solution obtained in the test for “Heavy metals” into a Nessler cylinder.
Standard preparation: Pipette out 2.0 ml of iron standard solution (20 ppm Fe) into 50 ml Nessler cylinder and dilute to 50 ml with water.
Procedure
Add to each cylinder, 2 ml of 20% iron free citric acid solution and 0.1 ml thioglycollic acid, mix, make alkaline with iron free ammonia solution and allow standing for 5 minutes. View down over a white surface. Any color produced by sample solution is not more intense than that produced by standard solution.

7. Sodium chloride
Limit: Not more than 7.0%
Reagent required
0.1M silver nitrate solution
Alcohol (80% v/v)
Procedure
Take accurately about 1.0 g. of the sample into a 100 ml conical flask, add 20 ml of alcohol (80% v/v), and shake for 10 minutes and filter. Repeat the operation four times. Dry the residue to constant mass at 100°C in the oven and set aside for the “Assay”. Combine the filtrates evaporate to dryness, take up (dissolve) the residue with water and dilute to 25.0 ml with the same solvent. Take 10.0 ml of this solution in a 250 ml conical flask; add 30 ml of water and 5 ml of dilute nitric acid. Titrate with 0.1M silver nitrate determining the end point potentiometrically, using a silver indicator electrode. 1 ml of 0.1M silver nitrate is equivalent to 5.844 mg of NaCl, calculate sodium chloride content using following formula
Calculation:
                                                          V x F x M x 25 x 100
% Sodium chloride content = ------------------------------                
                                                                 0.1 x W x 10
Where,
V = volume of 0.1 M Silver nitrate
F = Factor
M = Molarity of 0.1 M Silver nitrate
W = Weight of sample

8. Sodium glycolate
Limit: Not more than 2.0%
Reagent required
Glacial acetic acid
Acetone
Sodium chloride
Naphthalenediol reagent
0.062% w/v Glycolic acid
Sulphuric acid
Solution (A): In a 250 ml clean & dry conical flask take 0.2 g. of the sample, add 5 ml of glacial acetic acid, mix well and add 5 ml of water, continue stirring until complete dissolution. Slowly add 50 ml of acetone with stirring and then add 1g of Sodium chloride, filter wash the residue with acetone and dilute the filtrate to 100 ml with acetone.
Solution (B): Dissolve 0.310 g of glycollic acid, previously dried in vacuum over diphosphorus pentoxide, in water and dilute to 500.0 ml with the same solvent. To 5.0 ml of this solution, add 5 ml of acetic acid and allow standing for about 30 min. Add 50 ml of acetone and 1 g of sodium chloride and diluting to 100.0 ml with acetone.
Procedure
Transfer 2.0 ml of Solution (A) and Solution (B) in the two separate, open flasks; heat the flasks on a water bath for exactly 20 minutes. Cool and add 5 ml of Naphthalenediol reagent in each flask & mix thoroughly. Add a further 15 ml of the same reagent, mix, and cover the flask with aluminum foil and heat on a water bath for 20 minutes. Cool & dilute to 25 ml with sulphuric acid.
Take the absorbance of Solution (A) and Solution (B) at 540 nm using water as a blank. 
The absorbance of Solution (A) is not more than that of solution (B)

9. Microbial contamination
Limit: Free from Escherichia coli and Salmonellae
A. E.Coli
Medium required
Nutrient broth
Mac Coney’s broth
Peptone water
Kovac's reagent
Procedure
Place 1g of sample unless specified otherwise in 50ml of sterile nutrient broth and shake. Allow to stand one hour (four hours for gelatin) and shake again incubate at 37 + 1°c for 18 to 24 hours. Add 1 ml of the enrichment culture from above to a tube containing 5ml of Mac Conkey’s broth. Incubate at 37 + 1°c for 48 Hrs. and observe for acid and gas production in the test tube. On observation of acid and gas in the above carry out a secondary test by adding 1 g from the positive Mac Conkey’s into a) 5 ml of Mac Conkey’s both (b) 5 ml of peptone water. Incubate at 43.5° to 44.5° C for 24 hrs and examine for acid and gas in tube (a) & indole production in the tube (b). The presence of acid and gas and of indole in the secondary test indicates the presence of E.Coli. Carry out a control test by inoculating 10 to 50 cells of E.Coli (NCTC 9002) from a 24 hrs culture for the selective medium. The test is invalid if the control does not indicate the presence of E.Coli.
B. Salmonella
Medium required
Nutrient broth
Selenite F broth
Tetrathionate bile brilliant green broth                               
Bismuth Sulphite agar                                
Brilliant green agar                         
Triple sugar iron agar                                 
Urea broth
Procedure
Transfer 1g of sample unless specified otherwise to 100ml of sterile nutrient broth and shake. Allow standing for one hour (four hours for gelatin and shake again and incubate at 37+1° for 24 hours. Add 1.0ml of the enrichment culture from above to each of the two tubes containing to 10ml of Selenite F. broth and tetrathionate-bile brilliant green broth. Incubate at 37+1° for 48 hours.
From each of these two cultures, sub culture on Bismuth sulfite agar and brilliant green agar and incubate the plates at 37+1° for 18 to 24 hours. Observe black or green colonies on Bismuth sulfite agar and small transparent and colorless or opaque red zone colonies on Brilliant green agar. Sub culture any colony showing the above characteristics in triple sugar-iron agar and at the same time into a tube of urea broth. Incubate at 37+1°c for 18 to 24 hours. The formation of acid and gas in stab culture(With or without concomitant blackening) and the absence of acidity from the surface in T.S.I and absence of red color in the urea broth indicate the presence of salmonella.
Carry out the control test using 10 to 50 cells of Salmonella abony (NCTC 6017) from a 24 hours culture. The test is invalid if controls do not indicate the presence of salmonella.

10. Loss on Drying
Limit: Not more than 10.0%
Procedure
Weigh 1.000 g of substance in a clean and dried pre-weighed LOD Bottle. Cover the stopper and gently shake to distribute material to not more than 10 mm height. Place the LOD Bottle in an oven and remove the cover and leave it also inside the oven. Dry the sample at 105° C. On opening the chamber, immediately close the LOD Bottle, transfer it to desiccators and bring it to room temperature. Weigh up to constant weight.
Calculation:
                                         W2 – W3
% Loss on drying =    --------------- X 100
                                         W2 – W1
Where:                                                                                                                                      
W1 = Weight of empty clean and dried LOD Bottle
W2 = Weight of LOD Bottle + sample
W3 = Weight of LOD Bottle + sample (After drying)

11. Appearance of Solution
Color of solution
Reagent required
1 % w/v HCl
Yellow primary solution
Red primary solution
Blue primary solution
Reference solution (BS8): In a 100 ml volumetric flask, add 30 ml of Yellow primary solution, 30 ml of Red primary solution and 24 ml of Blue primary solution. Make up the volume to 100 ml with 1% w/v Hydrochloric acid. Dilute 1 ml of above solution to 100 ml with 1% w/v Hydrochloric acid, mix.
Sample solution: Centrifuge the suspension obtained from “Identification Test E” at 2500 RPM for 10 minutes. Carefully collect the supernatant liquid.
Procedure
Transfer to a flat bottomed test-tube of neutral glass, 15 to 25 mm in diameter, a suitable volume of the sample solution such that the test-tube is filled to a depth of 40 mm. Into another matched test-tubes add separately the same volume of water and Reference solution BS8.
Examine the columns of liquid in diffused light by viewing down the vertical axis of the tubes against a white background. The color intensity of the sample is same as that of water or is not greater than that of the reference solution.

Clarity of solution
Reagent required
10% w/v solution of hexamine
Hydrazine sulphate
Reference preparation: Dissolve 1.0 g of hydrazine sulfate in sufficient water to produce 100.0 ml and allow standing for 4 to 6 hours. Add 25.0 ml of this solution to 25 ml of 10% w/v solution of hexamine mix well and allow standing for 24 hours. Dilute 15.0 ml of the suspension to 1000.0 ml with water. Dilute 5.0 ml of this suspension to 100 ml with water.
Sample solution: Centrifuge the suspension obtained from ‘Identification Test E” at 2500 RPM for 10 minutes. Carefully collect the supernatant liquid.
Procedure
Into separate Nessler cylinder, place sufficient of the sample solution, water and of the reference suspension, freshly prepared, such that the Nessler cylinder is filled to a depth of 40 mm. After five minutes, compare the contents of the Nessler cylinder against a black background by viewing in diffused daylight down the vertical axes of the Nessler cylinder. The clarity of the sample preparation is not less than that of water or reference suspension.

12. Assay
Limit: NMT 2.8% and NMT 4.2% of sodium Na, calculated with reference to the material washed with the ethanol (95%) and dried.
Reagent required
Glacial acetic acid
0.1M Perchloric acid VS
Procedure
Weigh accurately 500 mg of the residue obtained in the test for “Sodium chloride” in a conical flask, add 80 ml of anhydrous glacial acetic acid, heat under a reflux condenser for 2 hours, and cool the solution to room temp.
Transfer to titration beaker and titrate with 0.1M Perchloric acid, determining end point potentiometrically. Each ml of 0.1M Perchloric acid is equivalent to 2.299 mg of Na. Carry out a blank titration and Calculate the sodium content using following formula.
Calculation:
                           V x F x M x 100
% Sodium = -----------------------
                                 0.1 x W
Where,
V = Consumed volume of 0.1 M Perchloric Acid
M= Molarity of 0.1 M Perchloric Acid
F = Factor                      
W= Weight of substance



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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