Determination of Solubility of a Drug substance

1.0 OBJECTIVE:

To lay down the procedure for determining the solubility of a drug substance in respective solvent / medium.

2.0 SCOPE:

This SOP is applicable for the determining the solubility of a drug substance in respective solvent / medium in Company Name

3.0 BACKGROUND:

Nil

4.0 RESPONSIBILITY:

4.1 Analytical Research personnel to carry out the experiments.

4.2 Group leader of Analytical Research to ensure the procedure to be followed.

4.3 Head of Analytical Research or his designee to ensure overall compliance.

5.0 PROCEDURE:

5.1 Take 50 mL of solvent / medium in which the solubility of the drug substance to be established into a 250 mL stoppered conical flask.

Note: 1) The volume of the solvent / medium and conical flask can be altered based on the requirement.

2) Solubility should be conducted in duplicate for respective solvent / medium.

5.2 Add an accurately weighed amount of drug substance, the amount to be added Initially can be determined based on any literature source or add 10 mg.

5.3 Mix the solution by swirling the conical flask to dissolve the material completely. If the material dissolves completely, go on adding weighed amounts of drug substance until the medium shows resistance towards dissolving the drug substance.

5.4 Sonicate for about 30 to 60 seconds to check the resistance. If the drug substance dissolves by sonication for about a minute, add further amounts.

5.5 If the drug substance does not dissolve completely even after about one minute sonication, add an excess amount of drug substance (about 500 mg) and sonicate for a period of 30 minutes.

1) Maintain the temperature of water in sonicator at about 25°C while sonication.

2) If the solubility of the Drug substance is found to be over 100 mg / mL by visual observation in a particular solvent / medium, the solubility experiment can be

stopped and the result should be reported as solubility more than 100 mg / mL.

5.6 If the drug substance added dissolves completely within 30 minutes, add further amounts and continue sonication.

5.7 After completion of 30 minutes sonication, filter the solution through 0.45 mm membrane filter.

5.8 Calculate the total amount of the drug substance added by adding all the amounts added (wt).

5.9 Estimate the content of the drug substance dissolved either by UV or HPLC method.

5.10 Prepare a standard solution preferably in the same medium. The concentration of the standard solution should be decided based on the easy solubility of the drug

substance. The concentration of the standard should be such that, at that level, the solubility of the drug substance should be complete and should give an optimum response.

5.11 Dilute the filtered test solution if necessary to get a concentration approximately equal to that of Standard preparation.

5.12 Calculate the amount of the drug substance dissolved by using the following formula:

5.13 The quantity of the drug substance dissolved in percentage.

Q= A x C x V x V2 x V4 x 100 \ B x Wt x V1 x V3

Where,

A = Response of the test solution.

B = Response of the standard solution

C = Concentration of standard solution in mg /mL

Wt = Total amount of drug substance added, in mg

V = Volume of the solvent / medium used for solubility, in mL

V1 =Volume of the filtered Test Solution taken, in mL

V2 = Diluted volume, in mL