according to Good Laboratory Practice (GLP) standards and that all data is accurately recorded and analyzed.

Regulatory Affairs Personnel: Ensure that the compatibility testing complies with relevant regulatory guidelines and that all documentation is prepared for regulatory submissions.

4) Procedure

The following steps outline the procedure for conducting compatibility studies between APIs and excipients:

1. Step 1: Selection of API and Excipients
   1. Identify the excipients to be tested based on the drug formulation requirements, such as binders, fillers, disintegrants, and preservatives.
   2. Select excipients that are compatible with the desired dosage form and meet regulatory standards for use in pharmaceutical formulations.
   3. Ensure that the excipients selected are appropriate for the intended route of administration (e.g., oral, topical, injectable) and the expected release profile of the drug product.
2. Step 2: Preparation of API-Excipient Mixtures
   1. Prepare the API-excipient mixtures in appropriate ratios based on the intended formulation.
   2. For solid dosage forms (e.g., tablets, capsules), blend the API with excipients to create homogeneous mixtures. For liquid formulations, prepare suspensions or solutions as needed.
   3. Ensure that each mixture is prepared under controlled conditions to avoid contamination and ensure consistency.
3. Step 3: Physical Compatibility Testing
   1. Conduct visual inspection of the API-excipient mixtures for any physical changes such as color changes, phase separation, or the formation of precipitates.
   2. Measure the flowability, compressibility, and hardness of the mixtures (for solid dosage forms) to assess any potential impact on the formulation process.
   3. Monitor for any physical changes over time, including the formation of aggregates or crystals, which may indicate incompatibility.
4. Step 4: Chemical Compatibility Testing
   1. Perform analytical tests, such as High-Performance Liquid Chromatography (HPLC), Fourier-Transform Infrared Spectroscopy (FTIR), or Differential Scanning Calorimetry (DSC), to identify any chemical interactions between the API and excipients.
   2. Evaluate the stability of the API in the presence of excipients over time, considering factors such as degradation products and API stability under various conditions (e.g., temperature, humidity).
   3. Analyze any chemical reactions that may occur between the excipient and the API, such as oxidation, hydrolysis, or complex formation.
5. Step 5: Stability Studies
   1. Store the API-excipient mixtures under various conditions (e.g., different temperatures, humidity levels, and light exposure) to simulate potential storage conditions for the final drug product.
   2. Monitor the mixtures for changes in physical appearance, chemical stability, and the presence of any degradation products.
   3. Perform long-term and accelerated stability testing to assess the shelf life of the drug formulation.
6. Step 6: Documentation and Data Analysis
   1. Document all observations, results, and test conditions during the compatibility studies. Include any deviations from the protocol, along with explanations for the deviations.
   2. Analyze the data to determine if any significant interactions or incompatibilities were detected. Based on the results, assess the suitability of the excipients for the formulation.
   3. Prepare a detailed report summarizing the compatibility studies, including conclusions and recommendations for excipient selection.
7. Step 7: Selection of Final Excipients
   1. Based on the compatibility study results, select the excipients that are most suitable for use in the final formulation.
   2. Ensure that the excipients chosen do not negatively impact the stability, bioavailability, or efficacy of the drug product.
   3. Document the final excipient selection and justify the choice based on compatibility, safety, and regulatory compliance.
8. Step 8: Sample Disposal
   1. Dispose of any remaining API-excipient mixtures and testing materials following appropriate safety protocols and environmental regulations.
   2. Ensure that hazardous materials are disposed of in designated waste containers to minimize environmental impact.

5) Documents

The following documents should be maintained during the compatibility studies between API and excipients:

1. Excipient Screening Protocols
2. API-Excipient Compatibility Test Records
3. Stability Study Reports
4. Analytical Testing Data (e.g., HPLC, FTIR, DSC)
5. Excipient Selection Reports
6. Sample Disposal Records

6) Abbreviations

• API: Active Pharmaceutical Ingredient
• HPLC: High-Performance Liquid Chromatography
• FTIR: Fourier Transform Infrared Spectroscopy
• DSC: Differential Scanning Calorimetry
• GLP: Good Laboratory Practices

7) References

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

• FDA Guidelines for Drug Excipients
• USP <701> on Excipient Testing
• ICH Q6A Specifications for Drug Substances and Drug Products

8) Version

Version 1.0: Initial version of the SOP.

9) Annexure

API-Excipient Compatibility Test Report Template

API ID	Excipient Name	Test Results	Observations	Final Conclusion