OBJECTIVE:
The objective of this study is to demonstrate the solubility data and dose solubility volume ratio.
SCOPE:
This SOP is applicable for the procedure to perform solubility test and its documentation.
RESPONSIBILITY:
- QC executive is responsible to perform solubility test analysis.
- QC Manager is responsible to ensure the implementation of SOP in solubility testing and its documentation.
PROCEDURE:
Solubility Data and Dose Solubility Volume:
- Criteria of Biopharmaceutics Classification System (BCS) system of APIs:
a. Aqueous solubility
b. Intestinal permeability
- API classification according to BCS as shown in below table
|
BCS Classification |
Solubility |
Permeability |
|
BCS class I |
High |
High |
|
BCS class II |
Low |
High |
|
BCS class III |
High |
Low |
|
BCS class IV |
Low |
Low |
- Solubility: The solubility class boundary is based on the highest strength of an IR product that is the subject of a biowaiver request. A drug substance is considered highly soluble when the highest strength is soluble in 250 mL or less of aqueous media within the pH range of 1 - 6.8 at 37 ± 1°C. The volume estimate of 250 mL is derived from typical BE study protocols that prescribe administration of a drug product to fasting human volunteers with a fluid ounce glass of water.
- The pH-solubility profile of the test drug substance should be determined at 37 ± 1°C in aqueous media with a pH 1.2, pH 4.5 and pH 6.8.
e.g., Highest Dose = 500mg, solubility (37°C) at pH 4.5 = 31.2 mg/mL
DSV = 500/31.2 = 16.03 mL
16.03mL < 250mL so highly soluble at pH 4.5
Procedure:
- Transfer an accurately weighed sample according to its highest dose strength in finished product, into a 250mL conical flask and add 250ml Standard buffer solution pH 1.2 and perform solubility at temperature 37 ± 1°C.
- After adding sample to the solvent immediately adjust pH of solution.
- The buffer solution pH 1.2 should heat at 37 ± 1°C using magnetic stirrer provides with heat. Wait for 30 minutes.
- The concentration of the drug substance in pH 1.2 should be determined using a validated assay method.
- Solution pH also measure at the end of the equilibrium solubility study.
- Repeat the same process mentioned above using USP acetate buffer pH 4.5 and USP phosphate buffer pH 6.8.
References:
- Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System. Guidance for Industry. U.S. Department of Health and Human Services. Food and Drug Administration.
- WORLD HEALTH ORGANIZATION. Proposal to waive in vivo bioequivalence requirements for the WHO model list of essential medicines immediate release, solid oral dosage forms. Geneva: WHO, 2005.
ABBREVIATIONS:
BCS – Biopharmaceutics Classification System
API - Active Pharmaceutical Ingredients
DSV – Dose Solubility Volume
REVISION HISTORY:
Nil
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