polymorph screening, ensuring that the procedures are followed as outlined and that data is accurately recorded.

Project Managers: Coordinate the polymorph screening activities and ensure that experiments are completed on time, within budget, and aligned with the overall drug development timeline.

Quality Control (QC): Ensure that all polymorph screening experiments are conducted under controlled conditions, and that results comply with regulatory standards and quality assurance procedures.

4) Procedure

The following steps outline the procedure for screening polymorphs of APIs:

1. Step 1: Selection of API
   1. Identify the API for polymorph screening. APIs that exhibit polymorphism are selected for this process, as different polymorphs can significantly affect the drug’s properties, such as solubility, bioavailability, and stability.
   2. Ensure that the API is well-characterized for its chemical structure and any known polymorphic forms.
2. Step 2: Selection of Solvents and Methods
   1. Choose appropriate solvents and conditions for crystallization based on the solubility and physical properties of the API.
   2. Select the crystallization techniques for screening, including solvent evaporation, cooling crystallization, and anti-solvent precipitation.
   3. Ensure that the selected methods allow for the formation of multiple polymorphs of the API under controlled conditions.
3. Step 3: Polymorph Formation
   1. Prepare API solutions in selected solvents under different conditions to induce the formation of polymorphs.
   2. Vary experimental conditions such as temperature, solvent, and evaporation rate to promote the crystallization of different polymorphs.
   3. Collect the solid forms and allow them to dry under controlled conditions.
4. Step 4: Polymorph Characterization
   1. Characterize the polymorphs using techniques such as X-ray diffraction (XRD), Differential Scanning Calorimetry (DSC), and Fourier-Transform Infrared Spectroscopy (FTIR) to determine their physical properties.
   2. Determine the solubility, melting point, and stability of each polymorph to assess its suitability for formulation development.
   3. Record and compare the characteristics of each polymorph to evaluate their potential impact on drug performance, such as dissolution rate and bioavailability.
5. Step 5: Selection of Suitable Polymorph
   1. Analyze the data to determine which polymorph provides the best balance of solubility, stability, and bioavailability.
   2. Choose the polymorph that exhibits the most favorable characteristics for formulation development, taking into consideration the intended route of administration and formulation type.
   3. Document the rationale for selecting the final polymorph for further development and testing.
6. Step 6: Stability Testing of Selected Polymorph
   1. Perform stability studies on the selected polymorph under various conditions (e.g., temperature, humidity, light exposure) to assess its long-term stability.
   2. Monitor any physical changes, such as polymorphic transitions or degradation, that may occur during the stability study period.
7. Step 7: Documentation and Reporting
   1. Document the results of the polymorph screening, including the experimental conditions, characterization data, and stability testing results.
   2. Prepare a detailed report summarizing the polymorph screening process, including findings, conclusions, and recommendations for the selection of the most suitable polymorph for formulation development.
   3. Ensure that all records are signed and dated, and stored securely in compliance with Good Laboratory Practice (GLP) standards.
8. Step 8: Sample Disposal
   1. Dispose of any remaining polymorph samples and testing materials following safety protocols and environmental regulations.
   2. Ensure that hazardous materials are disposed of in designated chemical waste containers to minimize environmental impact.

5) Documents

The following documents should be maintained during the polymorph screening process:

1. Polymorph Screening Protocol
2. API and Polymorph Preparation Records
3. Polymorph Characterization Data (XRD, DSC, FTIR)
4. Stability Testing Records
5. Data Analysis and Statistical Reports
6. Polymorph Screening Summary Report
7. Sample Disposal Records

6) Abbreviations

• API: Active Pharmaceutical Ingredient
• XRD: X-ray Diffraction
• DSC: Differential Scanning Calorimetry
• FTIR: Fourier-Transform Infrared Spectroscopy
• GLP: Good Laboratory Practices

7) References

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

• FDA Guidance for Pharmaceutical Development
• USP <711> on Polymorphism
• ICH Q6A Specifications for Drug Substances and Drug Products

8) Version

Version 1.0: Initial version of the SOP.

9) Annexure

Polymorph Screening Results Template

Polymorph ID	Characterization Method	Solubility Enhancement	Stability Test Results	Final Selection