Category: Limit Tests

List of Limit Test

1. Limit Test for Aluminium
2. Limit Test for Arsenic
3. Limit Test for Chloride
4. Limit Test for Heavy Metals 
5. Limit Test for Sulphates
6. Limit Test for Potassium
7. Limit Test for Iron
8. Limit Test for Lead
9. Limit Test for Clarity of solution
10. Limit Test for Colour of solution
11. General Identification Reactions of Ions and Functional Groups
12. Determination of sulphated Ash
13. Determination of Sulphur Dioxide
14. Determination of Acetyl Value
15. Determination of Saponification Value
16. Determination Acid Value and Ester Value
17. Determination of Hydroxyl Value
18. Determination of Iodine value
19. Determination of Peroxide Value
20. Limit Test for Selenium
21. Determination of Residue on Ignition
22. Determination of Melting Range or Temperature
23. Determination of Jelly Strength
24. Determination of pH
25. Determination of Freezing Point
26. Determination of Viscosity
27. Determination of Conductivity
28. Determination of Weight Per Millilitre and Relative Density (Specific Gravity)
29. Determination of Optical Rotation and Specific Optical Rotation
30. Determination of Refractive Index
31. Determination of Boiling Range or Temperature and Distillation Range  
32. Determination of Powder Fineness
33. Determination of Water by KF
34. Determination of Loss on Drying (LOD)
35. Determination of Bulk Density and Tapped Density of Powder
36. Volumetric Solutions

Title: Preparation and Standardisation of Volumetric Solutions

 

1. Objective: To provide documented procedures, instructions for the Preparation, Standardization and Shelf-life of Volumetric Solutions.

 

2. Scope:  This procedure is applicable for Preparation, Standardization and shelf life of Volumetric Solutions in QC Department.

 

3. Procedure:

• Volumetric solution should be prepared as mentioned in the respective Standard Testing Procedure or official monograph (IP, BP, and USP).
• Volumetric solutions should be prepared by accurately weighing a specified quantity & dissolving it to produce a specific volume.
• Volumetric solutions should be standardized by titration against a Primary Standard or by titration with a Standard Solution that has been recently standardized against a Primary Standard.
• Strength of the volumetric solutions should not deviate more than 10% of the prescribed strength.
• All volumetric solutions should be standardized in triplicate set & % RSD should not be more than 0.20 %.
• All the bottles should be labelled indicating the name, strength of the solution, date of preparation, signature of the person who prepared it, use before date, standardization due on, date of standardization.
• Records shall be maintained for each solution starting with the value determined when the solution was prepared & continuing with the values determined throughout the shelf life of the solutions in respective register.
• Shelf life of this solution is fifteen days to one month based on stability study of respective solution from the date of preparation. Discard the solution after self life or if observed hazy.
• Solutions of limited stability should be prepared on the day of use & discarded on completion of analysis.

 

5. Volumetric Solutions Preparation and Standardization:

List of Volumetric Solutions

Sr. No.	Name of Volumetric Solution	Strength
01	Ammonium Thiocyanate	0.1M
02	Ceric Ammonium Sulphate	0.1 M
03	Disodium Edetate	0.1 M / 0.01 M
04	Hydrochloric Acid	1 M
05	Iodine	0.05 M
06	Perchloric Acid	0.1M
07	Silver Nitrate	0.1 M
08	Sodium Hydroxide	1 M
09	Sodium Thiosulphate	0.1 M
10	Sulphuric Acid	0.5 M
11	Zinc Sulphate	0.1 M

 

1. 0.1 M Ammonium Thiocyanate:-

  

1. Preparation of Reagents:
   1. 1 M Silver Nitrate: Dissolve 1.7 g of Silver Nitrate in water and dilute up to 100 ml with water. (Preserve in Amber coloured bottle.)
   2. Ferric Ammonium Sulphate Solution (8.0 % w/v): Dissolve 8.0 g of Ferric Ammonium Sulphate in water and dilute up to 100 ml with water.

 

1. Procedure for Preparation of 1 M Ammonium Thiocyanate:

Dissolve 7.612 g of Ammonium Thiocyanate in sufficient water and dilute up to 1000 ml with water.

 

 

1. Procedure for Standardisation of 1 M Ammonium Thiocyanate:-

Pipette 30.0 ml of 0.1M Silver Nitrate into a glass-stoppered flask, dilute with 50 ml of water, add 2 ml of concentrated Nitric acid and 2 ml of Ferric Ammonium Sulphate Solution and titrate with the Ammonium Thiocyanate solution to the first appearance of a red-brown colour.

 

1. Calculation:

Determine the Molarity in triplicate.

Molarity   =   Volume of Silver Nitrate x  Molarity of Silver Nitrate

Volume of Ammonium Thiocyanate

 

1. Acceptance criteria:

The % RSD for triplicate determination of Molarity should not be more than 0.2%.

   

2.  0.1M Ceric Ammonium Sulphate

1. 1. Preparation of Reagents:
      1. Osmic Acid solution (1% w/v): Dissolve 1.0 g of Osmic acid in water and dilute up to 100 ml with water.
      2. Sodium Hydroxide Solution (8.0 % w/v): Dissolve 8.0 g of Sodium Hydroxide in water and dilute up to 100 ml with water.

• Dilute Sulphuric acid: Dilute 5.7 ml of Sulphuric acid to 100 ml with

1. Ferroin Sulphate Solution: Dissolve 0.7 g of Ferrous Sulphate and 1.5 g of 1,10- Phenanthroline Hydrochloride in 70 ml of water and add sufficient water to produce 100 ml.

Complies with the following test

Sensitivity: Add 0.1 ml of the solution and 0.15 ml of Osmic acid solution to 50 ml of 1 M Sulphuric Acid. Add 0.1 ml of 0.1 M Ceric Ammonium Sulphate the colour changes from red to light blue.

 

1. Procedure for Preparation of 1 M Ceric Ammonium Sulphate:

Dissolve 65 g of Ceric Ammonium Sulphate, with the aid of gentle heat, in a mixture of 30 ml  of   concentrated Sulphuric acid  and 500 ml of water.  Cool, filter the solution, if turbid and dilute to 1000 ml with purified water.

 

1. Procedure for Standardisation of 1 M Ceric Ammonium Sulphate:

Weigh accurately about 0.2 g of Arsenic trioxide, previously dried at 105°C for 1 hour, and transfer to a 500 ml conical flask. Wash down the inner inner walls of the flask with 25 ml of a 8.0 % w/v solution of Sodium Hydroxide, swirl to dissolve, add 100 ml water and mix. Add 30 ml of Dilute Sulphuric Acid, 0.15 ml of  Osmic Acid solution, 0.1 ml of Ferroin Sulphate solution until the pink colour is changed to very pale blue, adding the titrant slowly towards the end point.

1 ml of 0.1 M Ceric Ammonium Sulphate is equivalent to 0.004946 g of As₂O₃ (of Arsenic trioxide).

 

1. Calculation: Determine the Molarity in triplicate.

Molarity =  Weight of Arsenic Trioxide   x   0.1

————————————————————————

0.004946 x Burette reading in ml of Cerric Ammonium sulphate

 

1. Acceptance criteria:

The % RSD for triplicate determination of Molarity should not be more than 0.2%.

   

3. 0.1 M Disodium Edetate and 0.01 M Disodium Edetate:-

1. 1. Preparation of Reagents:
      1. Dilute Hydrochloric acid: Dilute 26 ml of Hydrochloric acid to 100 ml with water.
      2. Bromine Water: Freshly prepared saturated solution obtained by shaking occasionally during 24 hours 3 ml of Bromine with 100 ml of water and allow to separate. Store the solution over an excess of bromine in light resistant container.

• 2 M Sodium Hydroxide Solution: Dissolve 8.0 g of Sodium Hydroxide in sufficient water and dilute to 100 ml with water.

1. 10 M Ammonia: Dilute 75 ml of strong ammonia solution to 100 ml with
2. Ammonia Buffer pH 10.0: Dissolve 5.4 g of Ammonium Chloride in 20 ml of water, add 35 ml of 10 M Ammonia and dilute to 100 ml with water.
3. Mordant Black II (Eriochrome black T) Mixture: A mixture of 1 part of Eriochrome black T and 99 parts of Sodium Chloride.

Complies with following test.

Sensitivity: Dissolve 50 mg in 100 ml water, a brownish violet colour is produced. Add 0.3 ml of 6 M Ammonia; the colour changes to blue.  Add 0.1 ml of a 1 per cent w/v solution of Magnesium Sulphate, the colour changes to violet.

 

1. Procedure for Preparation of 1 M Disodium Edetate:

Dissolve 37.2 g of Disodium Edetate in sufficient water to produce 1000 ml.

 

1. Procedure for Preparation of 01 M Disodium Edetate:

Dissolve 3.72 g of Disodium Edetate in sufficient water to produce 1000 ml.

 

1. Procedure for Standardisation of 1 M Disodium Edetate:

Weigh accurately 0.8 g granulated Zinc, dissolve by gentle heating warming in 12 ml of Dilute Hydrochloric Acid and 0.1 ml of Bromine water. Boil to remove excess of Bromine, cool and add sufficient water to produce 200 ml. Pipette 20.0 ml of the resulting solution into a flask and nearly neutralise with 2 M Sodium Hydroxide. Dilute to about 150 ml with water, add sufficient Ammonia Buffer pH 10.0 to dissolve the precipitate and add 5 ml in excess. Add 50 mg of Mordant Black II Mixture and titrate with Disodium Edetate solution until the solution turn green.

1 ml of 0.1 M Disodium Edetate is equivalent to 0.00654 g of Zn (Zinc).   

 

1. Procedure for Standardisation of 01 M Disodium Edetate:

Weigh accurately 0.2 g granulated Zinc, dissolve by gentle heating warming in 3 ml of Dilute Hydrochloric Acid and 0.1 ml of Bromine water. Boil to remove excess of Bromine, cool and add sufficient water to produce 500 ml. Pipette 20.0 ml of the resulting solution into a flask and nearly neutralise with 2 M Sodium Hydroxide. Dilute to about 150 ml with water, add sufficient Ammonia Buffer pH 10.0 to dissolve the precipitate and add 5 ml in excess. Add 50 mg of Mordant Black II Mixture and titrate with Disodium Edetate solution until the solution turn green.

                                                                                                                                                                                                                                                                                                                                 

1. Calculation: (1 M Disodium Edetate)

Determine the Molarity in triplicate.

Molarity =  Weight of granulated Zinc x 0.1 x 20

——————————————————————————–

0.00654 x Burette reading in ml of Disodium Edetate x 200

 

1. Calculation: (01 M Disodium Edetate)

Determine the Molarity in triplicate.

Molarity =   Weight of granulated Zinc x 0.1 x 20

—————————————————————————–

0.00654 x Burette reading in ml of Disodium Edetate x 500

 

 

1. Acceptance criteria:

The % RSD for triplicate determination of Molarity should not be more than 0.2%.

 

4. 1 M Hydrochloric Acid :-

  

1. Preparation of Reagents:
   1. Methyl Red Solution: Dissolve 50 mg of Methyl Red powder in a mixture of 1.86 ml of 1 M Sodium Hydroxide and 50 ml of ethanol (95%). Shake well to dissolve and add sufficient water to produce 100 ml. (Colour change from Red to Yellow)

Complies with following test.       

Sensitivity: A mixture of 0.1 ml of the solution, 100 ml water and 0.05 ml of 0.02 M Hydrochloric acid is red. Not more than 0.1 ml of 0.02 M Sodium Hydroxide is required to change the colour to yellow.

 

1. Procedure for Preparation of 1 M Hydrochloric Acid:

Dilute 85 ml of concentrated Hydrochloric Acid with water to produce 1000 ml.

 

1. Procedure for Standardisation of 1 M Hydrochloric Acid:

Weigh accurately about 1.5 g of anhydrous Sodium Carbonate, previously heated at about 270°C for 1 hour. Dissolve it in 100 ml water and add 0.1 ml of Methyl Red solution. Solution colour is turn from colourless to yellow. Add Hydrochloric acid solution slowly from a burette, with constant stirring until the solution become faintly pink. Heat the solution to boiling, cool and continue the titration. Heat again to boiling and titrate further as necessary until the faint pink colour is no longer affected by continued boiling.

1 ml of 1 M Hydrochloric Acid is equivalent to 0.05299 g of Na₂CO₃ (Sodium Carbonate).

 

1. Calculation: Determine the Molarity in triplicate.

Molarity   =    Weight of Anhydrous Sodium Carbonate x 1

——————————————————————————-

0.05299 x Burette reading in ml of 1 M HCL

 

1. Acceptance criteria:

The % RSD for triplicate determination of Molarity should not be more than 0.2%.

 

 

5. 0.05 M Iodine:-

1. 1. Preparation of Reagents:
      1. Methyl Orange Solution: Dissolve 0.1 g of Methyl Orange 80 ml of water, add sufficient ethanol (95%) to produce 100 ml. (Colour change from Red to Yellow.)

Sensitivity: A mixture of 0.1 ml of the solution and 100 ml of water is yellow. Not more than 0.1 ml of 0.1 M Hydrochloric acid is required to change the colour to Red.

1. Starch solution : Triturate (Dissolve) 1 g of soluble Starch with 5 ml water and add under stirring 100 ml of boiling water containing 10 mg of mercuric iodide.

• Dilute Hydrochloric acid: Dilute 26 ml of Hydrochloric acid to 100 ml with water.

4. 1 M Sodium Hydroxide: Dissolve 4.0 g of Sodium Hydroxide in sufficient water and dilute to 100 ml with water.

1. Procedure for Preparation of 05 M Iodine:

Dissolve about 14 g of Iodine in a solution of 36 g of Potassium Iodide in 100 ml of water, add 3 drops of Hydrochloric acid and dilute with water to 1000 ml.

 

1. Procedure for Standardisation of 05 M Iodine:

Weigh accurately about 0.15 g of Arsenic Trioxide, previously dried at 105° for 1 hour, and dissolve in 20 ml of 1 M Sodium Hydroxide by warming, if necessary. Dilute with 40 ml of water, add 0.1 ml of Methyl Orange solution and add drop wise Dilute Hydrochloric acid until the yellow colour is changed to pink. Add 2 g of Sodium Carbonate, dilute with 50 ml of water and add 3 ml of Starch solution. Titrate with Iodine solution until a permanent blue colour is produced.

 

1 ml of 0.05 M Iodine is equivalent to 0.004946 g of As₂O₃ (Arsenic Trioxide).    

                                         

1. Calculation: Determine the Molarity in triplicate.

Molarity    =   Weight of Arsenic Trioxide x 0.05

—————————————————————

0.004946 x Burette reading in  ml of 0.05 M Iodine

 

1. Acceptance criteria:

The % RSD for triplicate determination of Molarity should not be more than 0.2%.

 

6. 0.1 M Perchloric Acid:-

1. 1. Preparation of Reagents:
      5. Crystal Violet solution: Dissolve 5.0 g of Crystal Violet in sufficient anhydrous glacial acetic acid and dilute to 100 ml with anhydrous glacial acetic acid.

[Colour change: Violet (basic) bluish green (neutral) and yellowish green/ Emerald green (acidic)].

Sensitivity: A mixture of 0.1 ml of the solution and 50 ml of Anhydrous Glacial Acetic Acid is bluish purple. Add 0.1 ml of 0.1 M Perchloric Acid: the solution turn bluish green.

 

1. Procedure for Preparation of 1 M Perchloric Acid:

Mix 8.5 ml of Perchloric acid with 500 ml of Anhydrous Glacial Acetic Acid and 25 ml of Acetic Anhydride, cool and add Anhydrous  Acetic Acid to produce 1000 ml. Allow the prepared solution stand for 1 day for the excess of Acetic Anhydride to be combined and carryout the determination of water. If the water content exceeds 0.05 %, add more Acetic Anhydride. If the solution contains not titratable water, add sufficient water to obtain a content of water between 0.02 per cent and 0.05 per cent. Allow the solution stand for 1 day and again titrate for water content. Standardize the solution in the following manner.

 

1. Procedure for Standardisation of 1 M Perchloric Acid:-

Weigh accurately about 0.35 g of Potassium Hydrogen Phthalate, previously powdered lightly and dried at 120°C for 2 hours and dissolve it in 50 ml of Anhydrous Glacial Acetic Acid. Add 0.1 ml Crystal Violet solution and titrate with the Perchloric Acid solution until the Violet colour changes to emerald green. Perform a blank determination and make any necessary correction.                                     1 ml of 1 M Perchloric Acid is equivalent to 0.02042 g of C₈H₅KO₄ (Potassium Hydrogen Phthalate).

 

1. Calculation: Determine the Molarity in triplicate.

Molarity   =    Weight of Potassium Hydrogen Phthalate x 0.1

——————————————————————

0.02042 x Burette reading in ml of 0.1 M Perchloric Acid

 

1. Acceptance criteria:

The % RSD for triplicate determination of Molarity should not be more than 0.2%.

7. 0.1 M Silver Nitrate:-

1. 1. Preparation of Reagents:
      5. Eosin solution: Dissolve 5.0 g of Eosin in sufficient water and dilute to 100 ml with

 

1. Procedure for Preparation of 1 M Silver Nitrate:

Dissolve 17.0 g Silver Nitrate in sufficient water to produce 1000 ml.

 

1. Procedure for Standardisation of 1 M Silver Nitrate:

Weigh accurately about 0.1 g of Sodium Chloride, previously dried at 110°C for 2 hours and dissolve in 5 ml of water. Add 5 ml of Acetic Acid, 50 ml of Methanol and 0.15 ml of Eosin solution. Stir, preferably with magnetic stirrer, and titrate with the 0.1 M Silver Nitrate solution until permanent pink precipitate is produced.                                          1 ml of 0.1 M Silver Nitrate is equivalent to 0.005844 g of NaCl (Sodium Chloride).

1. Calculation: Determine the Molarity in triplicate.

Molarity   =     Weight of Sodium Chloride x 0.1

——————————————————

0.005844 x Burette reading in ml of 0.1 M Silver Nitrate

 

1. Acceptance criteria:

The % RSD for triplicate determination of Molarity should not be more than 0.2%.

 

8. 1 M Sodium Hydroxide:-

1. 1. Preparation of Reagents:
      1. Phenolphthalein solution: Dissolve 1.0 g of Phenolphthalein in sufficient ethanol (95%) and dilute to 100 ml with ethanol (95%). (Colour change: Colourless to Red.)

Sensitivity: A mixture of 0.1 ml of the solution and 100 ml of water is colourless. Not more than 0.2 ml of 0.02 M Sodium Hydroxide is required to change the colour to pink.

 

 

1. Procedure for Preparation of 1 M Sodium Hydroxide:

Dissolve 42.0 g of Sodium Hydroxide in sufficient water to produce 1000 ml.

 

1. Procedure for Standardisation of 1 M Sodium Hydroxide:

Weigh accurately about 5.0 g of Potassium Hydrogen Phthalate, previously powdered and dried at 120°C for 2 hours and dissolve in 75 ml of water. Add 0.1 ml Phenolphthalein solution and titrate with the Sodium Hydroxide solution until a permanent pink colour is produced.                                                                                                                                 Each 1 ml of 1 M sodium Hydroxide is equivalent to 0.2042 g of C₈H₅KO₄ (Potassium Hydrogen Phthalate). 

 

1. Calculation: Determine the Molarity in triplicate.

Molarity  = Weight of Potassium Hydrogen Phthalate x 1.0

———————————————————————-

0.02042 x Burette reading in ml of 1 M Sodium Hydroxide

 

1. Acceptance criteria:

The % RSD for triplicate determination of Molarity should not be more than 0.2%.

 

9. 0.1 M Sodium Thiosulphate

1. 1. Preparation of Reagents:
      1. Starch Solution: Triturate (Dissolve) 1 g of soluble Starch with 5 ml water and add under stirring, 100 ml of boiling water containing 10 mg of mercuric iodide.
      2. 2 M Hydrochloric Acid: Dilute 17 ml of Conc. Hydrochloric acid to 100 ml with

 

1. Procedure for Preparation of 0.1 M Sodium Thiosulphate:

Dissolve 25.0 g of Sodium Thiosulphate and 0.2 g of Sodium Carbonate in water and dilute to 1000 ml.

 

1. Procedure for Standardisation of 0.1 M Sodium Thiosulphate:

Weigh accurately 0.200 g of Potassium Bromate and dissolve in sufficient water to produce 250.0 ml. To 50.0 ml of this solution add 2 g of Potassium Iodide and 3 ml of 2 M Hydrochloric acid and titrate with the 0.1 M Sodium Thiosulphate solution using Starch solution, added towards the end of the titration, as indicator until the blue colour is discharged.                                                                                                 1 ml of 0.1 M Sodium Thiosulphate is equivalent to 0.002784 g of KBrO₃ (Potassium Bromate).     

 

1. Calculation: Determine the Molarity in triplicate.

Molarity   =   Weight of Potassium Bromate x 0.1 x 50

———————————————————–

0.002784 x Burette reading in ml of 0.1 M Sodium Thiosulphate x 250

 

1. Acceptance criteria:

The % RSD for triplicate determination of Molarity should not be more than 0.2%.

 

10. 0.5 M Sulphuric Acid:-

1. 1. Preparation of Reagents:
      1. Methyl Red Solution: Dissolve 50 mg of Methyl Red powder in a mixture of 1.86 ml of 1 M Sodium Hydroxide and 50 ml of ethanol (95%). Shake well to dissolve and add sufficient water to produce 100 ml. (Colour change from Red to Yellow)

Complies with following test.       

Sensitivity: A mixture of 0.1 ml of the solution, 100 ml water and 0.05 ml of 0.02 M Hydrochloric acid is red. Not more than 0.1 ml of 0.02 M Sodium Hydroxide is required to change the colour to yellow.

 

1. Procedure for Preparation of 0.5 M Sulphuric Acid:

Add slowly, with stirring, 28 ml of Sulphuric Acid to 1000 ml of water, allow to cool 25° and standardise the solution in the following manner.

 

1. Procedure for Standardisation of 0.5 M Sulphuric Acid:

Weigh accurately about 1.5 g of anhydrous Sodium Carbonate, previously heated at about 270°C for 1 hour. Dissolve it in 100 ml water and add 0.1 ml of Methyl Red solution. Solution colour is turn from colourless to yellow. Add Hydrochloric acid solution slowly from a burette, with constant stirring until the solution become faintly pink. Heat the solution to boiling, cool and continue the titration. Heat again to boiling and titrate further as necessary until the faint pink colour is no longer affected by continued boiling.

1 ml of 0.5 M Sulphuric Acid is equivalent to 0.05299 g of Na₂CO₃ (Sodium Carbonate).

1. Calculation: Determine the Molarity in triplicate.

Molarity   =   Weight of Anhydrous Sodium Carbonate x 1

—————————————————————-

0.05299 x Burette reading in ml of 0.5 M Sulphuric Acid

 

1. Acceptance criteria:

The % RSD for triplicate determination of Molarity should not be more than 0.2%.

 

11. 0.1 M Zinc Sulphate :-

1. 1. Preparation of Reagents:
      11. 2 M Acetic acid: Dilute 11.4 ml of Glacial Acetic Acid to 100 ml with water.

 

1. Procedure for Preparation of 0.1 M Zinc Sulphate:

Dissolve 29.0 g of Zinc Sulphate in sufficient water and dilute to 1000 ml with water.

 

1. Procedure for Standardisation of 0.1 M Zinc Sulphate:-

Take 20.0 ml of 0.1 M Zinc Sulphate solution into a 500 ml conical flask, add 5 ml of 2 M Acetic acid and dilute to 200 ml with water. Add about 50 mg of Xylenol Orange Mixture and Hexamethylenetetramine until the solution becomes violet-pink. Add 2 g of Hexamethylenetetramine in excess. Titrate with 0.1 M Disodium Edetate until the violet-pink colour changes to yellow.

1 ml of 0.1 M Disodium Edetate is equivalent to 0.02875 g of ZnSO_4,7H₂O (Zinc Sulphate).

 

1. Calculation: Determine the Molarity in triplicate.

Molarity   =    Burette reading in ml of Disodium Edetate x Molarity of Disodium Edetate

————————————————————–

Volume of 0.1 M Zinc Sulphate

 

1. Acceptance criteria:

The % RSD for triplicate determination of Molarity should not be more than 0.2%.

 

 

---

 

“End of Document”

Title: Determination of Bulk Density and Tapped Density of  Powder

 

1.      Objective: Determination of Bulk Density and Tapped Density of powder.

 

2.      Principle: The bulk density of a powder is the ratio of the mass of an untapped powder sample and its volume including the contribution of inter particulate void volume. Hence, the bulk density depends on both the density of powder particles and the spatial arrangement of particles in the powder bed. The bulk density is expressed in grams per ml (g/ml).

 

3. Procedure:

The bulking properties of a powder are dependent upon the preparation, treatment, and storage of the sample, i.e., how it was handled. The particles can be packed to have a range of bulk densities; however, the slightest disturbance of the powder bed may result in a changed bulk density. Thus, the bulk density of a powder is often very difficult to measure with good reproducibility and, in reporting the results, it is essential to specify how the determination was made. The bulk density of a powder is determined by measuring the volume of a known weight of powder sample, that may have been passed through a sieve, into a graduated cylinder (Method I), or by measuring the mass of a known volume of powder that has been passed through a volumeter into a cup (Method II) or a measuring vessel (Method III).  Method I and Method III are favored.

 

 

 

• Method I: Measurement in a Graduated Cylinder

Pass a quantity of material sufficient to complete the test through a sieve with apertures greater than or equal to 1.0 mm, if necessary, to break up agglomerates that may have formed during storage; this must be done gently to avoid changing the nature of the material.  Into a dry graduated 250-ml cylinder (readable to 2 ml) introduce, without compacting, approximately 100 g of test sample, M, weighed with 0.1% accuracy. Carefully level the powder without compacting, if necessary, and read the unsettled apparent volume (V₀) to the nearest graduated unit. Calculate the bulk density in g/ml by the formula M/V₀. Generally, replicate determinations are desirable for the determination of this property. If the powder density is too low or too high, such that the test sample has an untapped apparent volume of either more than 250 ml or less than 150 ml, it is not possible to use 100 g of powder sample. Therefore, a different amount of powder has to be selected as the test sample, such that its untapped apparent volume is 150–250 ml (apparent volume greater than or equal to 60% of the total volume of the cylinder); the weight of the test sample is specified in the expression of results. For test samples having an apparent volume between 50 ml and 100 ml, a 100-ml cylinder readable to 1 ml can be used; the volume of the cylinder is specified in the expression of results.

                      

                       Bulk density (g/ml)=  M/V_o

 

 

Where, M = Weight of sample powder.

                   V_o = unsettled volume measured on the cylinder.

• Method II: Measurement in a Volumeter
• Apparatus:

The apparatus (Figure 1) consists of a top funnel fitted with a 1.0-mm sieve The funnel is mounted over a baffle box containing four glass baffle plates over which the powder slides and bounces as it passes. At the bottom of the baffle box is a funnel that collects the powder and allows it to pour into a cup of specified capacity mounted directly below it. The cup may be cylindrical (25.00 ± 0.05 ml volume with an inside diameter of 30.00 ± 2.00 mm) or square (16.39 ±0.2 ml volume with inside dimensions of 25.400 ±0.076 mm).

 

Figure-1

 

• Procedure:

Allow an excess of powder to flow through the apparatus into the sample receiving cup until it overflows, using a minimum of 25 cm³ of powder with the square cup and 35 cm³ of powder with the cylindrical cup. Carefully scrape excess powder from the top of the cup by smoothly moving the edge of the blade of a spatula perpendicular to and in contact with the top surface of the cup, taking care to keep the spatula perpendicular to prevent packing or removal of powder from the cup. Remove any material from the sides of the cup, and determine the weight (M) of the powder. Calculate the bulk density, in g/ml, by the formula:

.                                  Bulk Density (g/ml) =  M/ V_o

 

in which V₀ is the volume in ml of the cup. Record the average of three determinations using three different powder samples.

• Method III: Measurement in a vessel
• Apparatus:

The apparatus consists of a 100-ml cylindrical vessel of stainless steel with dimensions as specified.

 

• Procedure:

Pass a quantity of powder sufficient to complete the test through a 1.0-mm sieve, if necessary, to break up agglomerates that may have formed during storage, and allow the obtained sample to flow freely into the measuring vessel until it over flows. Carefully scrape the excess powder from the top of the vessel as described for Method II. Determine the weight (M₀) of the powder by subtraction of the previously determined mass of the empty measuring vessel. Calculate the bulk density (g/ml) by the formula M₀/100, and record the average of three determinations using three different powder samples.

Bulk Density (g/ml) =   M₀ /100

 

 

• TAPPED DENSITY:

The tapped density is an increased bulk density attained after mechanically tapping a container containing the powder sample. Tapped density is obtained by mechanically tapping a graduated measuring cylinder or vessel containing a powder sample. After observing the initial powder volume or weight, the measuring cylinder or vessel is mechanically tapped, and volume or weight readings are taken until little further volume or weight change is observed. The mechanical tapping is achieved by raising the cylinder or vessel and allowing it to drop under its own weight a specified distance by either of three methods as described below. Devices that rotate the cylinder or vessel during tapping may be preferred to minimize any possible separation of the mass during tapping down.

 

 

 

• Method I:

The apparatus consists of the following:

A 250-ml graduated cylinder (readable to 2 ml with a mass of 220 ± 44 g)

A settling apparatus capable of producing, in 1 min,  either nominally 250 ± 15 taps from a height of  3 ± 0.2 mm, or nominally 300 ± 15 taps from a height of 14 ± 2 mm. The support for the graduated cylinder, with its holder, has a mass of 450 ± 10 g.

 

Procedure:

Proceed as described above for the determination of the bulk volume (V₀). Secure the cylinder in the holder. Carry out 10, 500, and 1250 taps on the same powder sample and read the corresponding volumes V10, V500, and V1250 to the nearest graduated unit. If the difference between V500 and V1250 is less than 2 ml or equal to 2 ml, V1250 is the tapped volume. If the difference between V500 and V1250 exceeds 2 ml, repeat in increments such as 1250 taps, until the difference between succeeding measurements is less than  or equal to 2 ml. Fewer taps may be appropriate for some powders, when validated. Calculate the tapped density (g/ml) using the formula m/V_F, in which V_F is the final tapped volume. Generally, replicate determinations are desirable for the determination of this property. Specify the drop height with the results. If it is not possible to use a 100-g test sample, use a reduced amount and a suitable 100-ml graduated cylinder (readable to 1 ml) weighing 130 ±16 g and mounted on a holder weighing 240 ±12 g. The modified test conditions are specified in the expression of the results.

 

Tapped Density (g/ml) =    m/V_F

 

 

Where m: sample weight  and V_F: final tapped volume

  

• Method II

Apparatus and Procedure: Proceed as directed under Method I except that the mechanical tester provides a fixed drop of 3 ± 0.2 mm at a nominal rate of 250 taps per minutes.

 

• Method III

Apparatus and Procedure: Proceed as directed in Method III—Measurement in a Vessel for measuring bulk density using the measuring vessel equipped with the cap  is lifted 50–60 times per minute by the use of a suitable tapped density tester. Carry out 200 taps, remove the cap, carefully scrape excess powder from the top of the measuring vessel as described in Method III—Measurement in a Vessel for measuring the bulk density. Repeat the procedure using 400 taps. If the difference between the two masses obtained after 200 and 400 taps exceeds 2%, carry out a test using 200 additional taps until the difference between succeeding measurements is less than 2%. Calculate the tapped density (g/ml) using the formula M_F/100, where M_F is the mass of powder in the measuring vessel. Record the average of three determinations using three different powder samples. The test conditions including tapping height are specified in the expression of the results

Tapped Density (g/ml) = M_F   / 100

 

Where M_F: Mass of the powder

 

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Title: Determination of Loss on Drying

 

1.      Objective: To determine the Loss on drying in the sample.

 

2. Principle:

• Loss on drying is the loss in weight in % w/w resulting from water and volatile matter of any kind that can be driven off under specified conditions.
• Thermogravimetry is a technique in which the weight of a sample is recorded as a function of temperature according to a controlled temperature programme.

        

4. Procedure:

The test is carried out on a well-mixed sample of the substance. If the substance is in the form of large crystals, reduce the size by rapid crushing to a powder.

Where the drying temperature is indicated by a single value, dry at the prescribed temperature ± 2°C.

Unless otherwise specified in the individual monograph, use Method A.

 

• Method A:

Weigh a glass-stoppered, shallow weighing bottle that has been dried under the same conditions to be employed in the determination. Transfer to the bottle the quantity of the sample specified in the individual monograph, cover it and accurately weigh the bottle and the contents. Distribute the sample as evenly as practicable by gentle sidewise shaking to a depth not exceeding 10 mm. Place the loaded bottle in the drying chamber (oven or desiccator) as directed in the monograph, remove the stopper and leave it also in the chamber. Dry the sample to constant weight or for the specified time and at the temperature indicated in the monograph. After drying is completed, open the drying chamber, close the bottle promptly and allow it to cool to room temperature (where applicable) in a desiccator before weighing. Weigh the bottle and the contents.

1. “In a desiccator”: dry over phosphorous pentoxide at a atmospheric pressure and at room temperature;

NOTE: Care must be taken to keep the desiccant fully effective by frequent replacement.

1. “ in vacuo” dry over phosphorous pentoxide at a pressure of 1.5 kPa to 2.5 kPa  at room temperature;
2. “in vacuo” with a specified temperature range”:dry over phosphorous pentoxide at a pressure of 1.5 kPa to 2.5 kPa with temperature range given in the monograph;
3. in an oven in a specified temperature range”:dry in an oven within the range given in the monograph;
4. “under high vacuum ”: dry over phosphorous pentoxide at a pressure of 0.1.5 kPa  at the given in the monograph;

 

Calculation:

Weight of empty LOD Bottle:  W₁

Weight of LOD Bottle + sample: W₂

Weight of sample:  W₃ (W₂ – W₁)

Weight of LOD Bottle + sample (After dying): W₄

Weight Loss: W₅ (W₂ – W₄)

 

% Loss on drying =    W₅   x 100_____

W₃

 

• Method B:

Thermogravimetry: Thermogravimetry is a technique in which the weight of a sample is recorded as a function of temperature according to a controlled temperature programme.

 

• Apparatus:

A thermobalance consisting of a device for heating or cooling the substance being examined according to a given temperature programme, a sample holder in a controlled atmosphere, an electrobalance and a recorder. The instrument may be coupled to a device permitting the analysis of volatile products.

• Temperature verification: Check the temperature scale using nickel or other suitable material according to the manufacturer’s instruction.
• Calibration of the Electrobalance: Place a suitable quantity of calcium oxalate monohydrate RSin the sample holder and record the weight. Set the heating rate according to the manufacturer’s instructions and start the temperature programme. Record the thermogravimetric curve as a graph with temperature on the abscissa, increasing from left to right, and weight on the ordinate, increasing upwards. Stop the rise in temperature at 230°. Measure the distance on the graph between the initial and final weight-temperature plateaux that corresponds to the loss of weight. The declared loss of weight for calcium oxalate monohydrate RS is stated on the label.

NOTE: If the apparatus is in frequent use, carry out temperature verification and calibration regularly. Otherwise, carry out such checks before each measurement.

• Procedure:

Apply the same procedure to the substance being examined, using the conditions prescribed in the monograph. Calculate the loss of weight of the substance being examined from the distance measured on the graph obtained and express as a percentage w/w of the substance taken.

The actual procedure and the calculations to be employed are dependent on the particular instrument used. Consult the manufacture’s literature and/or the thermal analysis literature for the most appropriate technique for a given instrument. In any event, it is imperative to keep in mind the limitations of solid solution formation, insolubility in the melt, polymorphism and decomposition during the analysis.

 

 

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Title: Determination of Water by KF

 

1.      Objective: To measure the amount of Water content in the sample.

 

2. Principle: The Titrimetric determination of water by the Karl Fischer method depends on the reaction that takes place quantitatively between water and a reagent consisting of sulfur dioxide and iodine in anhydrous pyridine and usually methanol. The reaction is carried out in a suitable solvent such as methanol.

 

3. Procedure:

• Method I: Titrimetric Method:
• Karl Fischer reagent (KF) reagent:

The reagents and solutions used for preparing the KF reagent should be kept anhydrous and care should be taken throughout the determination to prevent exposure to atmospheric moisture. The reagent should be protected from light and stored in a bottle to which is fitted an automatic burette.

• Primary Standardisation of the reagent:

Place about 36 ml of dehydrated methanol in the titration vessel and add sufficient Karl Fischer reagent to give the characteristics end-point. Add quickly 150 to 350 mg of Sodium Tartrate, C₄H₄O₆Na₂, 2H₂O, accurately weighed by difference and titrate to the endpoint.

The water equivalence factor F, in mg of water per ml of the reagent is given by the expression 0.1566 x (w/v).

Where, w is the weight in mg of the Disodium Tartrate and v is the volume in ml of the reagent required.

• Secondary Standardisation of the reagent:

The Karl Fisher reagent may alternatively be standardised for each day’s use against a water-methanol solution standardised as follows. Add 2.0 ml of water to 1000.0 ml of dehydrated methanol. Retain a portion of the methanol used for a blank determination. Place 25 ml, accurately measured of the water methanol solution in the titration vessel and titrate with Karl Fisher reagent. Perform a blank titration on 25 ml accurately measured, of the methanol used and make any necessary correction. The water content in mg per ml of the water methanol solution is given by the expression VF/25 in which V is the volume in ml of Karl Fischer reagent required and F is the water equivalent factor of the reagent determined against Disodium Tartrate as directed under Primary standardisation of the reagent.

            Water content of water methanol solution:   V x F__

25

• Apparatus:

A titration vessel of about 60 ml capacity is fitted with two platinum electrodes, about 0.05 sq. cm in area and about 2.5 cm apart a nitrogen inlet tube, a stopper which accommodates the burette tip and a vent tube protected by a suitable desiccant such as phosphorous pentoxide or silica gel. The substance being examined is introduced through an inlet or side arm which can be closed by a ground stopper. Stirring is done magnetically or by means of a stream of dried nitrogen passed through the solution during the titration. The air in the entire system should be kept dry during the titration.

The end point is determined by amperometry. The circuit consists of a potentiometer of about 2000 ohms. Connected across a 1.5 v battery. The resistance is adjusted so that an initial low current passes through the electrodes. On adding the reagent the needle of the microammeter  shows a deflection but returns immediately to its starting  position. At the end point of the titration a slight excess of the reagent produces a deflection which persists for not less than half a minute.

The actual procedure to be employed are dependent on the particular instrument used. Refer the manufacture’s literature and/or the analysis literature for the most appropriate technique for a given instrument.

Use Method A unless otherwise directed.

• Method A:

Unless otherwise directed add about 20 ml of dehydrated methanol to the titration vessel and titrate to the electrometric end point with the Karl Fischer reagent. Transfer quickly the prescribed amount of the substance being examined, accurately weighed to the titration vessel. Stir for 1 minute and titrate again to the electrometric end point using the Karl Fischer reagent.

The water content of the sample, in mg is given by the expression S x F, in which S is the volume, in ml of the Karl Fischer reagent used to titrate the sample and F is the water equivalent factor.

 

Water Content (%w/w) =  S x F x 100______

Weight of sample

 

• Method B:

This method should be followed for samples that react with difficulty or too slowly for convenient direct titration with the Karl Fischer reagent.

Unless otherwise directed add about 10 ml of dehydrated methanol to the titration vessel and titrate to the electrometric end point with the Karl Fischer reagent. Transfer quickly the prescribed amount accurately weighed, of the substance being examined to the titration vessel followed by an accurately measured amount of Karl Fischer reagent sufficient to given an excess of about 1 ml. Allow to stand , protected from light, for 1 minute, stirring well. Titrate the excess of the reagent to the electrometric endpoint with dehydrated methanol to which has been added an accurately known amount of water equivalent to about 0.25% w/v.

Calculate the content of water from the expression S x F, where S is the volume in ml, of the KF reagent  used to titrate the sample and F is equivalence factor.

Unless otherwise directed, express the result as a percentage w/w.

 

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Title: Determination of Powder Fineness

 

1. Objective: To determine powder fineness by sieve test method.

 

2. Principle: Powder fineness may be classified by determining the smallest sieve opening through which a specified quantity of material passes.

 

3. Procedure:

Test procedures for sieving powder materials are described under Particle Size Distribution Estimation by Analytical Sieving, and, where practical, the particle size distribution should be estimated by this procedure. The classification of powder fineness in this Pharmacopeia, expressed in descriptive terms, is provided in the table. For practical reasons, sieves are the preferred means of measuring powder fineness for most pharmaceutical purposes. Sieving is most suitable where a majority of the particles are larger than about 75 µm, although it can be used for some powders having smaller particle sizes where the method can be validated. Avoid processing conditions that would alter the true particle size distribution of the powder being tested.

Powdered Vegetable and Animal Drugs: In determining the powder fineness of a vegetable or animal drug, no portion of the drug may be rejected during milling or sifting unless specifically permitted in the individual monograph.

Air Permeation Method for Determining Fineness of Sub-sieve Size Particles: The average particle size measured is in the range of 0.2 to 50 µm. The test specimen is loaded into a precision bore tube and is compacted between two paper disks and porous plugs by a rack-and-pinion packing plunger. The determination of the particle size of the specimen in the uniformly packed column is based on its resistance to the flow of a closely regulated current of dried air. The liquid level of a flowmeter-manometer corresponds directly to particle size. Special handling instructions and procedures are provided in the individual monographs.

Classification of Powder Fineness: Powder fineness may be classified by determining the smallest sieve opening through which a specified quantity of material passes. Results are typically reported as the following:

d₉₀ = smallest sieve opening through which 90% or more of the material passes
d₅₀ = smallest sieve opening through which 50% or more of the material passes
d₁₀ = smallest sieve opening through which 10% or more of the material passes.

 

The upper and lower limit of the sieve opening values may be reported when results of two or more test lots are combined, e.g., “Lot A has a d₅₀ value of 1000 µm with a range of 850–1180 µm.”

An alternative but less informative method of classifying powder fineness is by use of the terms in the following table.

Classification of Powders by Fineness

Classification of Powder	d50 Sieve Opening (µm)
Very Coarse	> 1000
Coarse	355–1000
Moderately Fine	180–355
Fine	125–180
Very Fine	90–125

 

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Title: Determination of Boiling Range or Temperature and Distillation Range  

 

1. Objective: This test method provides a method of measurement of Boiling Range or Temperature and Distillation range of liquids.

 

2. Principle: The Boiling Range or Temperature and Distillation range is the temperature interval, corrected for a pressure of 101.3 kPa, within which a liquid, or a specified fraction of a liquid, distils under the conditions specified in the test. This test method covers the determination of Boiling or Distillation range of liquids boiling between 30°C and 350°C, that are chemically stable during the distillation process, by manual or automatic distillation procedures. This test method is applicable to organic liquids such as hydrocarbons, oxygenated compounds, chemical intermediates, and blends thereof.

 

3. Procedure:

• Apparatus:

The apparatus ( Figure -1) consists of a round bottom distillation flask (A),  a straight tube condenser (B) which fits on to the side arm of the flask and a plain-bend adaptor (C) attached to the end of the condenser. The lower end of the condenser may be bent to provide a delivery tube, or it may be connected to a bent adopter that serves as a delivery tube. A calibrated thermometer is inserted in the neck of the flask so that the upper end of the mercury reservoir is 5 mm lower than the junction of the lower wall of the lateral tube. The thermometer is graduated at 0.2 ° intervals and the scale covers a range of about 50°. During the determination, the flask, including its neck, is protected from draughts by a suitable screen.

• Method:

If the liquid under examination distills below 80°C, cool it to between 10°C and 15°C before measuring the sample for distillation. Assemble the apparatus and place in the flask 100 ml of the liquid being examined, taking care not to allow any any liquid to enter the side-arm.  Insert the thermometer and shield the entire heating and flask assembly from external air currents. Add few pieces of porous material and heat rapidly to boiling using Bunsen burner (or electric heater or heating mantle) and an asbestos plate pierced by a hole 33 mm in diameter. Record the temperature at which the first drop of distillate falls into the receiver and adjust the rate of heating

to obtain a regular distillation rate of 4-5 ml per minute. Record the temperature when the last drop of liquid evaporates from the lowest point in the distillation flask or when specified percentage has distilled over. Correct the observed temperature reading for any variation in barometric pressure from the normal (101.3kPa) using the following expression

t₁ = t₂+K (a-b)

where      t₁  = the corrected temperature

t₂ = the observed temperature

  a = 101.3 when the barometric pressure is measured in kilopascals (kPa) or 760 when  measured in torr.

b = barometric pressure at the time of determination (refer below table)

K = correction factor indicated in table

 

Variation of correction factor with temperature.

 

Boiling Range	KPa	Ktorr
Less than 100	0.30	0.040
100-140	0.34	0.045
141-190	0.38	0.050
191-240	0.41	0.055
More than 240	0.45	0.060

 

 

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Title: Determination of Refractive Index  

 

1. Objective: To determine the Refractive Index of liquid material.

 

2. Principle: The Refractive Index (n) of a substance with reference to air is the ratio of the sine of the angle of incidence to the sin of the angle of refraction of a beam of light passing from air into the substance. It varies with the wavelength of the light used in its measurement.

 

3. Procedure:

Unless otherwise specified in the individual monograph, the refractive index, n_D²⁰ is measured at 20⁰ ± 0.5⁰ with reference to the wavelength of the D line of sodium (l =589.3 nm). The temperature should be carefully adjusted and maintained since the refractive index varies significantly with temperature.

The Abbe Refractometer is convenient for most measurements of refractive index but other refractometers of equal or greater accuracy may be used. Commercial refractometer is normally constructed for use with white light but are calibrated to give the refractive index in terms of the D line of sodium. The apparatus is provided with a water jacket to control the temperature of measurement. The manufacturer’s instruction relating to a suitable light source should be followed subject to the directions given in the Pharmacopoeia. To achieve accuracy of ±0.0001, the apparatus should be calibrated against distilled water which has a refractive index of 1.3330 at 20° and 1.3325 at 25° or against the reference liquids given in Table 1.

Table 1

Reference Liquid	nD20	Temperature Coefficient     n /   t
Carbon tetrachloride	1.4603	– 0.00057
Toluene	1.4969	– 0.00056
α -Methylnaphthalene	1.6176	– 0.00048

*Refractive index value for the D line of Sodium measured at 20°

 

NOTE – The cleanliness of the instrument should be checked frequently by determining the refractive index of distilled water.

 

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Title: Determination of Optical Rotation and Specific Optical Rotation

 

1. Objective: To determine the Optical Rotation and Specific Optical Rotation of the solutions and solvents.

 

2. Principle: There are 2 types of plane polarized light [PPL], 1) Right circularly plane polarized light (RCPL), 2) Left circularly plane polarized light (LCPL). They are equal and opposite direction. When a PPL is pass through the optical active compound, due to its circular birefringence results unequal rate of propagation of left and right circularly polarized rays. This unequal rate of propagation of both RCPL and LCPL deviates the PPL from its original direction and it is called to be ‘Optical Rotation’.

Optical Activity: The compounds which are having the ability to rotate the plane of polarised light are called optically active compounds .They rotate plane of polarized light due to their chirality (asymmetric character) this phenomenon is known as ‘optical activity’.  When a ray of monochromatic polarized light strikes a solution, several phenomenon’s occurs like:-1. Reflection on the surface. 2. Refraction. 3. Rotation of plane polarization 4. Absorption.

 

3. Procedure:

• Definitions:
• Optical Rotation: The optical rotation of a substance is the angle through which the plane of polarisation is rotated when polarised light passes through the substance, if liquid, or a solution of the substance. Substances are described as dextro-rotatory or laevo-rotatory according to whether, [α]_D²⁵ the plane of polarisation is rotated clockwise or anticlockwise, respectively as determined by viewing towards the light source. Dextro-rotation is designated (+) and laevo-rotation is designated (-).
• Specific Optical Rotation of Liquid: The specific optical rotation,[α]_D²⁵ of a liquid substance is the angle of rotation α , of the plane of polarisation at the wavelength of the D line of sodium (l = 589.3 nm) measured at 25° , unless otherwise specified, calculated with reference to a 1-dm thick layer of the liquid, and divided by the specific gravity at  25⁰
• Specific Optical Rotation of Solid: The specific optical rotation, [α]_D²⁵,of a solid substance is the angle of rotation, α , of the plane of polarisation at the wavelength of the D line of sodium (l = 589.3 nm) measured at 25⁰C, unless otherwise specified, calculated with reference to a 1-dm thick layer of a solution containing 1 g of the substance per ml. The specific optical rotation of a solid is always expressed with reference to a given solvent and concentration.

 

• Apparatus:

A commercial instrument constructed for use with a sodium lamp and capable of giving readings to the nearest 0.02° is suitable for most purposes. For certain applications, the use of a photoelectric polarimeter capable of taking measurement at the specific wavelengths may be necessary.

The accuracy and precision of optical rotation measurements can be increased if the following precautions are taken.

1. a) The instrument must be in a good condition. The optical elements must be very clean and in exact alignment. The match point should be close to the normal zero mark.

(b) The light source should be properly aligned with respect to the optical bench. It should be supplemented by a filtering system capable of isolating the D line from sodium light.

(c) Specific attention should be paid to temperature control of the solution and of the polarimeter.

(d) Differences between the initial readings or between observed and corrected optical rotation, calculated, as either specific optical rotation or optical rotation, should not be more than one-fourth of the range specified in the monograph for the substance.

(e) Polarimeter tubes should be filled in such a way as to avoid air bubbles. Particular care is necessary for semi-micro or micro tubes.

(f) For tubes with removable end plates fitted with gaskets and caps, tighten the end-plates only enough to ensure a leak-proof seal between the end plate and the body of the tube.

(g) For substances with low rotatory power, the end-plates should be loosened and tightened again after each reading, in the measurement of both the rotation and the zero point.

(h) Liquids and solutions of solids must be clear.

 

• Calibration:

The apparatus may be checked by using a solution of previously dried sucrose and measuring the optical rotation in a 2-dm tube at 25° and using the concentrations indicated in Table 1.

Table 1

Concentration (g/100 ml)	Angle of Rotation (+)  at 25o
10.0	13.33
20.0	26.61
30.0	39.86
40.0	53.06

 

• Method:

The optical rotation, unless otherwise specified, is measured at the wavelength of the D line of sodium (l = 589.3 nm) at 25°, on a layer 1 dm thick. It is expressed in degrees.

• For Solids:

Weigh accurately a suitable quantity of the substance being examined to obtain the solution of the strength specified in the individual monograph and transfer to a volumetric flask by means of water or other solvent, if specified. If a solvent is used, reserve a portion of it for the blank determination. Unless otherwise specified, adjust the contents of the flask to 25°C by suspending the flask in a constant-temperature bath. Make up to volume with the solvent at 25°C and mix well. Transfer the solution to the polarimeter tube within 30 minutes from the time the substance was dissolved and during this time interval maintain the solution at 25°C. Determine the zero point of the polarimeter and then make five readings of the observed rotation of the test solution at 25°C. Take an equal number of readings in the same tube with the solvent in place of the test solution. The zero correction is the average of the blank readings, and is subtracted from the average observed rotation if the two figures are of the same sign or added if they are opposite in sign to obtain the corrected observed rotation.

• For Liquids:

Unless otherwise specified, adjust the temperature of the substance being examined to 25°C, transfer to a polarimeter tube and proceed as described for solids, beginning at the words “Determine the zero point…”

 

• Calculations:

Calculate the specific optical rotation using the following formulae, dextro-rotation and laevo-rotation being designated by (+) and (-) respectively.

For liquids [α]_D²⁵ = α/ld ²⁵

For solids [α]_D²⁵ = 100α /lc

Where α = corrected observed rotation, in degrees, at 25°C.

D = D line of sodium light (l = 589.3 nm)

l  = length of the polarimeter tube in dm

d²⁵ ₂₅ = specific gravity of the liquid or solution at 25°

c  = concentration of the substance in % w/v

 

NOTE: The requirement for optical rotation and specific optical rotation in the Pharmacopoeia apply to a dried, anhydrous or solvent-free material in all those monographs in which standards for loss on drying, water, or solvent content respectively are given. In calculating the result, the loss on drying, water or solvent content determined by the method specified in the monograph is taken into account.

 

 

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Title: Determination of Weight Per Millilitre and Relative Density (Specific Gravity)

 

1. Objective: To determine the Weight per ml and Relative Density of the solutions and solvents.

 

2. Principle: The Weight per millilitre is determined by dividing fill weight of test liquid in gram by the capacity of pycnometer expressed in ml at the specified temperature.

3.       Procedure:

3.1        Definitions:

• Specific Gravity: It is based on the ratio of the weight of a liquid in air at 25^oC to that of an equal volume of water at the same temperature. Where a temperature is specified in the individual monograph, the Specific Gravity is the ratio of the weight of a liquid in air at specified temperature to that of an equal volume of water at the same temperature.
• Relative Density: It is defined as the mass of a unit volume of the substance at 25^oC expressed in g, of the quantity of liquid that fills a pycnometer at the specified temperature to that of an equal volume of water at the same temperature.

 

• Method: (Weight per ml)

Select a thoroughly clean and dry pycnometer that previously has been calibrated by determining its weight and the weight of recently boiled and cooled water contained in it at 25°C. Adjust the temperature of the test liquid to about 20°C and fill the pycnometer with it. Adjust the temperature of the filled pycnometer to 25°C, remove any excess liquid, and weigh. When the monograph specifies a temperature different from 25°C, filled pycnometers must be brought to the temperature of the balance before they are weighed. Subtract the tare weight of the pycnometer from the filled weight of the pycnometer.

Determine the weight per ml by dividing the weight of test liquid in gram by the capacity of pycnometer expressed in ml at the specified temperature.

 

• Method: (Relative Density)

Proceed as described under weight per millilitre method. Divide the weight of the substance in the pycnometer by the weight of water contained in the pycnometer, both determined at 25°C, unless otherwise specified in the individual monograph.

 

 

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