Standard Operating Procedure for Preformulation Studies for Capsule Dosage Forms

Department	Capsule Manufacturing
SOP No.	SOP/CM/021/2025
Supersedes	SOP/CM/021/2022
Page No.	Page 1 of 8
Issue Date	01/02/2025
Effective Date	05/02/2025
Review Date	01/02/2026

1. Purpose

This SOP defines the procedures for conducting preformulation studies for capsule dosage forms to ensure the selection of suitable excipients, formulation parameters, and to optimize the development process for capsule formulations.

2. Scope

This SOP applies to all preformulation studies for capsule dosage forms, including studies on APIs, excipients, physical characteristics, and compatibility assessments.

3. Responsibilities

• Formulation Development Team: Responsible for conducting preformulation studies, selecting excipients, and formulating capsule dosage forms based on the findings of the studies.
• Quality Control (QC) Team: Ensures that preformulation studies comply with quality standards and verifies the quality and compatibility of excipients and APIs.
• Quality Assurance (QA) Team: Oversees compliance with this SOP and ensures that the preformulation studies are documented properly and according to regulatory requirements.
• Regulatory Affairs: Ensures that the preformulation studies meet regulatory requirements and are aligned with the submission guidelines for regulatory approval.

4. Accountability

The Formulation Development Supervisor is accountable for ensuring that all preformulation studies are conducted as per the SOP. The QA Manager is responsible for ensuring compliance with regulatory requirements and maintaining proper documentation.

5. Procedure

5.1 Selection of Active Pharmaceutical Ingredient (API)

The first step in preformulation studies is the selection of the appropriate API for the capsule formulation:

1. API Characteristics
   1. Review the physicochemical properties of the API, including solubility, stability, and hygroscopicity, to ensure it is suitable for capsule formulation.
   2. Conduct a stability study on the API under various conditions to determine its shelf life and compatibility with other ingredients.
2. API Selection Criteria
   1. Ensure that the selected API meets regulatory standards and is compatible with the capsule shell and excipients used in the formulation.
   2. Confirm that the API is available in the required quantities and forms for manufacturing and scale-up purposes.

5.2 Excipients Selection

Select appropriate excipients for the capsule formulation based on the characteristics of the API:

1. Excipients Compatibility Study
   1. Conduct compatibility studies between the API and excipients to identify potential interactions or incompatibilities.
   2. Use techniques like Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), and HPLC to assess the chemical stability of the API when combined with excipients.
2. Excipients Functionality
   1. Choose excipients that fulfill the functional requirements of capsule formulations, such as fillers, binders, lubricants, and disintegrants.
   2. Ensure that the selected excipients are compatible with the manufacturing process and do not interfere with the API’s bioavailability.

5.3 Powder Flow and Compaction Studies

Conduct studies to assess the flow properties and compaction behavior of the powdered formulation:

1. Flow Properties
   1. Evaluate the flow properties of the powdered blend using tests like bulk density, tapped density, Hausner ratio, and angle of repose.
   2. Ensure that the powder blend flows consistently and uniformly, ensuring uniform filling of capsules during manufacturing.
2. Compaction Studies
   1. Conduct compaction studies to assess the tabletability and compressibility of the powder blend. This ensures that the blend can form a consistent capsule shell without defects.
   2. Assess the hardness, friability, and dissolution characteristics of the compacted material to confirm that it meets the required specifications for capsule dosage forms.

5.4 Solubility and Dissolution Studies

Conduct solubility and dissolution studies to evaluate the API’s bioavailability:

1. Solubility Studies
   1. Determine the solubility of the API in different solvents to identify the most appropriate solvent for the formulation.
   2. Use various techniques such as UV-Vis spectrophotometry or HPLC to quantify the solubility and ensure adequate bioavailability of the API.
2. Dissolution Studies
   1. Conduct dissolution testing to assess how the API will be released from the capsule shell once ingested.
   2. Ensure that the dissolution profile meets the required specifications for effective drug delivery.

5.5 Stability Studies

Conduct stability studies to determine the shelf life of the capsule formulation:

1. Stability Testing Conditions
   1. Subject the capsule formulation to various storage conditions, including accelerated stability testing at high temperatures and humidity levels.
   2. Monitor the physical, chemical, and microbiological properties of the formulation to ensure that it remains stable throughout its shelf life.
2. Stability Study Results
   1. Document the results of stability testing, including changes in appearance, dissolution, and potency, and determine the shelf life of the formulation.
   2. Adjust the formulation or manufacturing process if necessary based on the stability results to ensure the product remains within specifications.

5.6 Documentation of Preformulation Studies

Ensure that all findings from the preformulation studies are properly documented:

1. Study Reports
   1. Compile all data from the preformulation studies into a comprehensive report, including details of API and excipient selection, compatibility studies, dissolution results, and stability testing.
   2. Ensure that the reports are reviewed and approved by the formulation development team and the QA team before progressing to the next stage of formulation development.
2. Record Keeping
   1. Maintain all records of preformulation studies for future reference, audits, and regulatory submissions.
   2. Ensure that all records are stored securely and comply with Good Documentation Practices (GDP).

6. Abbreviations

• SOP: Standard Operating Procedure
• API: Active Pharmaceutical Ingredient
• QA: Quality Assurance
• QC: Quality Control
• GMP: Good Manufacturing Practice
• HPLC: High-Performance Liquid Chromatography
• UV-Vis: Ultraviolet-Visible Spectroscopy

7. Documents

1. Preformulation Study Report (Annexure-1)
2. API and Excipient Compatibility Study (Annexure-2)
3. Solubility and Dissolution Study Results (Annexure-3)

8. References

• ICH Q1A (R2) – Stability Testing of New Drug Substances and Products
• USP <711> – Dissolution Testing
• FDA Guidance for Industry: Dosage Form Development

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Preformulation Study Report

Date	Study Name	Result Summary	Action Taken
02/02/2025	API Compatibility Study	No incompatibilities found	Proceeded to excipient selection

Annexure-2: API and Excipient Compatibility Study

Date	API	Excipient	Compatibility Test	Result
02/02/2025	API-123	Excip-456	DSC, FTIR	Compatible

Annexure-3: Solubility and Dissolution Study Results

Date	API	Solubility in Water	Dissolution Rate
02/02/2025	API-123	0.5 mg/mL	85% release in 30 mins

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
01/01/2024	1.0	Initial Version	New SOP Creation	QA Head
01/02/2025	2.0	Updated preformulation study procedures	Standardization and clarity	QA Head