and oily vehicles suitable for IM administration.

2. Scope

This procedure applies to all personnel involved in formulation development activities for intramuscular injections within the Sterile Injectable Manufacturing unit, including pre-formulation trials, excipient selection, and product evaluation.

3. Responsibilities

• Formulation Scientist: Designs trial formulations, evaluates physical and chemical properties, and documents batch development.
• Analytical Development Team: Performs viscosity, pH, and particle size testing.
• QA Team: Verifies formulation protocols and ensures documentation compliance.
• R&D Manager: Approves final formulation and directs development strategy.

4. Accountability

The Head of Formulation Development is accountable for compliance with this SOP and for ensuring scientific justification of selected excipients and formulation strategy.

5. Procedure

5.1 Pre-Formulation Studies

1. Determine solubility of API in:
   • Water and buffers (pH 3–8)
   • Oily vehicles (e.g., sesame oil, castor oil)
   • Co-solvents (e.g., benzyl alcohol, ethanol)
2. Assess chemical stability in selected media at various temperatures.
3. Study polymorphic forms for suspension formulations.

5.2 Formulation Design

1. Select formulation type:
   • Aqueous solution (e.g., for water-soluble drugs)
   • Suspension (e.g., for poorly soluble drugs)
   • Oily solution/suspension (e.g., depot formulations)
2. Design for controlled viscosity (15–30 cP) to ensure injectability.
3. Incorporate:
   • Viscosity enhancers (e.g., methylcellulose)
   • Suspending agents (e.g., polysorbate 80)
   • Buffers, isotonicity adjusters, and preservatives if needed

5.3 Trial Batch Preparation

1. Use laminar airflow bench to prepare lab-scale batches (100–500 mL).
2. Filter aqueous formulations using 0.22 µm filters before filling.
3. For suspensions, ensure uniform dispersion and test for sedimentation and redispersibility.

5.4 Analytical & Stability Evaluation

1. Conduct following tests on each trial batch:
   • pH, osmolality, viscosity, specific gravity
   • Particle size (for suspensions)
   • Sterility and endotoxin (for sterile batches)
2. Place trial batches on stability as per ICH Q1A (Annexure-1).

5.5 Documentation

1. Document composition, process, and evaluation in Formulation Development Record (Annexure-2).
2. Prepare summary report with rationale for excipient selection (Annexure-3).

6. Abbreviations

• IM: Intramuscular
• API: Active Pharmaceutical Ingredient
• QA: Quality Assurance
• ICH: International Council for Harmonisation
• cP: Centipoise (unit of viscosity)

7. Documents

1. Stability Testing Data Sheet – Annexure-1
2. Formulation Development Record – Annexure-2
3. Excipient Justification Summary – Annexure-3

8. References

• ICH Q8 (R2) – Pharmaceutical Development
• USP Chapter <789> – Particulate Matter in Injections
• WHO TRS 961 Annex 6 – Good Practices for Sterile Pharmaceutical Products

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation	Formulation Scientist	QA Officer	Head – Formulation Development
Department	R&D	Quality Assurance	Formulation Development

11. Annexures

Annexure-1: Stability Testing Data Sheet

Date	Batch ID	Storage Condition	pH	Viscosity (cP)	Observations	Analyst
12/06/2025	IM-DEV-002	30°C/65% RH	6.2	28	Stable	Sunita Reddy

Annexure-2: Formulation Development Record

Batch No.	IM-DEV-002
Formulation Type	Oil-based suspension
Key Ingredients	API X, Castor oil, Benzyl alcohol
Prepared By	Ajay Mehta
Date	10/06/2025

Annexure-3: Excipient Justification Summary

Excipient	Function	Justification
Castor Oil	Vehicle	Approved oil for depot injection, enhances solubility
Benzyl Alcohol	Preservative	Effective against microbial growth in multi-dose vials

Revision History

Revision Date	Revision No.	Details	Reason	Approved By
12/04/2022	1.0	Initial Issue	New SOP	QA Head
18/06/2025	2.0	Updated excipient scope and annexures	Annual Review	QA Head