Standard Operating Procedure for Incorporation of Solubility Enhancers in Lyophilized Products
1) Purpose
This SOP outlines the method of incorporating solubility enhancers into lyophilized formulations to improve the dissolution of poorly soluble active pharmaceutical ingredients (APIs) after reconstitution.
2) Scope
This SOP applies to formulation scientists, production operators, and QA personnel involved in the preparation, testing, and verification of lyophilized formulations that require solubility enhancers to achieve the desired dissolution profile.
3) Responsibilities
- Formulation Scientists: Responsible for identifying suitable solubility enhancers based on the solubility characteristics of the API.
- Operators: Responsible for incorporating solubility enhancers into the formulation according to the Batch Manufacturing Record (BMR).
- QA Personnel: Responsible for validating the incorporation of solubility enhancers and ensuring the documentation is accurate and complete.
4) Procedure
4.1 Selection of Solubility Enhancers
4.1.1 Criteria for Selection
- 4.1.1.1 Solubility enhancers must increase the dissolution rate of the API without causing instability or precipitation. Common solubility enhancers include cyclodextrins, surfactants like polysorbates, or hydrotropic agents such as urea.
4.2 Incorporation of Solubility Enhancers
4.2.1 Weighing and Addition
- 4.2.1.1 Accurately weigh the solubility enhancers using a calibrated balance as specified in the BMR.
- 4.2.1.2 Add the solubility enhancers to the formulation solution during the preparation phase and ensure complete dissolution through gentle stirring.
4.2.2 Mixing and Homogenization
- 4.2.2.1 Stir the solution using a mechanical stirrer until the solubility enhancers are evenly dispersed throughout the formulation.
- 4.2.2.2 Homogenize the mixture if necessary to ensure consistency in solubility enhancement.
4.3 Filtration and Filling
- 4.3.1 Filter the solution through a sterile 0.22-micron filter to ensure it is free of particulates before filling into sterile vials.
- 4.3.2 Aseptically fill the vials with the filtered solution, ensuring accurate volume measurement.
4.4 Lyophilization and Post-Lyophilization Testing
- 4.4.1 Load the filled vials into the lyophilizer and run the freeze-drying cycle as per the BMR.
- 4.4.2 After lyophilization, reconstitute the product and test for the dissolution rate of the API to ensure that the solubility enhancers are functioning as expected.
4.5 Documentation
Document all steps, including weighing, addition, mixing, filtration, and lyophilization in the Solubility Enhancer Logbook. Ensure QA verification for every step.
5) Abbreviations
- BMR: Batch Manufacturing Record
6) Documents
- Solubility Enhancer Logbook
7) References
- Pharmacopoeial guidelines for enhancing solubility in pharmaceutical formulations
8) SOP Version
Version 1.1
Annexure
Solubility Enhancer Logbook Template
| Date | Solubility Enhancer Name | Batch No. | Quantity | Operator Initials | QA Verification |
|---|---|---|---|---|---|
| DD/MM/YYYY | Enhancer Name | Batch Number | Quantity (g) | Operator Name | QA Initials |