the defined timelines and that results are communicated to the relevant teams.

Quality Assurance (QA): Review and verify that solubility tests are conducted in compliance with Good Laboratory Practice (GLP) standards and internal quality guidelines.

Regulatory Affairs Personnel: Ensure that the solubility testing complies with regulatory guidelines and that the data generated is suitable for inclusion in regulatory submissions.

4) Procedure

The following steps outline the procedure for solubility testing of drug candidates:

1. Step 1: Selection of Solvents
   1. Review the chemical properties of the drug candidate to select appropriate solvents for testing. Common solvents include water, ethanol, methanol, and buffer solutions.
   2. Ensure that the selected solvents are capable of solubilizing the drug candidate within the expected concentration range.
   3. If required, select a series of solvents with varying polarity to determine the solubility in different environments (e.g., aqueous and organic solvents).
2. Step 2: Preparation of Solutions
   1. Weigh the drug candidate accurately to prepare solutions at different concentrations in the selected solvent(s).
   2. Prepare solutions in a clean glass container or appropriate vessel, ensuring that the drug is fully suspended or dissolved before starting the test.
   3. If necessary, warm the solution gently to aid in dissolution, but ensure the temperature does not exceed the drug’s stability limit.
3. Step 3: Solubility Testing
   1. For each test, measure a fixed volume of the prepared solution and allow it to equilibrate for a predetermined amount of time (typically 24 hours) at the desired temperature (e.g., room temperature or controlled temperature).
   2. Use a suitable mixing method, such as shaking or stirring, to ensure that the drug candidate and solvent are adequately mixed during the testing period.
   3. After equilibration, filter the solution to remove any undissolved particles or precipitates that may be present.
4. Step 4: Analytical Measurements
   1. Quantify the solubility of the drug candidate by measuring the concentration of dissolved drug in the solvent. Use a suitable analytical technique such as High-Performance Liquid Chromatography (HPLC), UV-Vis spectroscopy, or another method based on the properties of the drug.
   2. For UV-Vis or spectrophotometric methods, measure the absorbance of the solution at the drug’s maximum absorption wavelength and calculate the concentration using a calibration curve.
   3. Ensure that appropriate calibration standards and controls are used to ensure accurate and reliable measurements.
5. Step 5: Data Recording and Reporting
   1. Record the solubility results, including the concentration of dissolved drug, solvent used, temperature, time, and any deviations from the standard procedure.
   2. Compare the solubility results with the expected solubility of the drug candidate to assess its suitability for further formulation development.
   3. Prepare a summary report that includes the solubility data, any observations, and conclusions regarding the solubility of the drug candidate in the tested solvents.
6. Step 6: Quality Control and Validation
   1. Perform quality control checks to ensure that the solubility testing process is consistent and that the results are reproducible across multiple test runs.
   2. Validate the analytical method used for solubility determination by comparing it with known standards or by conducting method precision and accuracy studies.
   3. Ensure that the solubility results are properly documented and that the data is retained for future reference and regulatory compliance.
7. Step 7: Storage of Formulations
   1. Store the remaining solubility testing samples under the appropriate conditions (e.g., in a refrigerator or at room temperature) to preserve sample integrity for any future testing or analysis.
   2. Label all stored samples with relevant information such as sample ID, solvent used, and testing conditions.
8. Step 8: Sample Disposal
   1. Dispose of any remaining solvents, samples, and laboratory waste following safety protocols and environmental regulations.
   2. Ensure that hazardous materials, including solvents and chemicals, are disposed of in appropriate waste containers.

5) Documents

The following documents should be maintained during the solubility testing of drug candidates:

1. Solubility Testing Protocols
2. Formulation and Solvent Preparation Records
3. Analytical Data and Calibration Curves
4. Quality Control and Validation Reports
5. Test Results and Summary Reports
6. Sample Disposal Records

6) Abbreviations

• HPLC: High-Performance Liquid Chromatography
• UV-Vis: Ultraviolet-Visible
• QC: Quality Control
• GLP: Good Laboratory Practices

7) References

References to regulatory guidelines and scientific literature that support this SOP:

• OECD Guidelines for Good Laboratory Practice (GLP)
• USP Chapter <811> on Solubility
• ICH Q6A Specifications for Drug Substances and Drug Products

8) Version

Version 1.0: Initial version of the SOP.

9) Annexure

Solubility Testing Log

Sample ID	Solvent Used	Concentration (mg/mL)	Temperature (°C)	Test Date	Results