Creams: SOP for Pre-formulation Studies of Cream Products – V 2.0

Standard Operating Procedure for Pre-formulation Studies of Cream Products

Department	Creams
SOP No.	SOP/CRM/033/2025
Supersedes	SOP/CRM/033/2022
Page No.	Page 1 of 6
Issue Date	09/08/2025
Effective Date	14/08/2025
Review Date	09/08/2026

1. Purpose

The purpose of this Standard Operating Procedure (SOP) is to define the process for conducting pre-formulation studies for cream products. Pre-formulation studies provide critical data regarding the compatibility, stability, and functionality of the ingredients in the formulation, guiding the development of stable, effective, and safe cream products.

2. Scope

This SOP applies to all cream products being developed within the Creams Department. It covers the evaluation of raw materials, excipients, APIs, and the formulation process prior to the final product development and commercial production.

3. Responsibilities

Formulation Development Team: Responsible for selecting the ingredients, developing the initial formulations, and conducting the pre-formulation studies.
Quality Control (QC): Responsible for conducting tests to assess the properties of raw materials, formulations, and excipients, and for evaluating their suitability for use in cream formulations.
Quality Assurance (QA): Ensures that the pre-formulation studies are conducted according to this SOP and are compliant with GMP standards and regulatory guidelines.
Regulatory Affairs: Ensures that all raw materials and formulations comply with regulatory requirements and standards for the intended market.

4. Accountability

The Head of Creams Manufacturing is responsible for overseeing the pre-formulation studies process. The QA Manager is accountable for ensuring that all pre-formulation data are reviewed and compliant with regulatory and internal quality standards.

5. Procedure

5.1 Selection of Raw Materials and Excipients

Review the specifications for the active pharmaceutical ingredients (APIs) and excipients that will be used in the formulation. Ensure they are of appropriate quality and comply with regulatory standards.
Select excipients based on their compatibility with the APIs and the desired product characteristics (e.g., texture, stability, and spreadability). Common excipients include emulsifiers, thickeners, preservatives, and stabilizers.
Obtain samples of raw materials and conduct physical and chemical testing to assess their suitability for use in the formulation. Testing should include:
- Particle size distribution
- Solubility and compatibility with the chosen solvent(s)
- Stability under various storage conditions
- Purity and identity testing (e.g., for APIs)

5.2 Formulation Development

Develop preliminary cream formulations by combining the selected APIs and excipients in the desired concentrations. The formulation should be based on the desired therapeutic and cosmetic properties of the product (e.g., moisturizing, anti-aging).
Prepare small-scale batches of each formulation to evaluate the physical properties of the cream, such as texture, spreadability, and sensory feel.
Record detailed formulation records, including ingredient quantities, equipment used, processing conditions, and any observations during formulation preparation.

5.3 Evaluation of Physical Properties

Evaluate the physical properties of the cream formulations, which may include:
- Viscosity: Use a viscometer to measure the viscosity of the cream at different stages of development to ensure that the desired texture is achieved.
- pH: Measure the pH of the cream to ensure it falls within the acceptable range for topical use.
- Spreadability: Assess how easily the cream spreads on the skin. This is important for user comfort and product efficacy.
- Appearance: Evaluate the cream’s color, clarity, and consistency to ensure it meets the desired standards.
If the cream formulation does not meet the desired criteria for any of these physical properties, make the necessary adjustments to the formulation (e.g., altering excipient concentrations, adding thickeners or emulsifiers).

5.4 Stability Testing

Conduct initial stability testing on the pre-formulation batches to assess how the cream performs under varying environmental conditions (e.g., temperature, humidity, light exposure). This helps identify potential issues with product stability early in the development process.
Stability tests should include:
- Real-time stability testing at normal storage conditions
- Accelerated stability testing at higher temperatures to simulate long-term storage
- Freeze-thaw cycling to assess the effect of temperature fluctuations on the formulation
Document all stability test results, including any observed changes in the cream’s physical properties, such as texture, separation, or color changes.

5.5 Compatibility Testing

Perform compatibility studies to ensure that the selected ingredients, including APIs and excipients, do not interact negatively with each other. This includes testing for:
- Chemical compatibility: Ensure that no chemical reactions occur between ingredients that would lead to the degradation of the product.
- Physical compatibility: Check that the cream does not show signs of separation or instability.
- Microbial compatibility: Ensure that preservatives and other ingredients do not interfere with the antimicrobial efficacy of the formulation.
Record all compatibility study results and modify the formulation or ingredients as needed if any issues arise.

5.6 Documentation of Pre-formulation Studies

Document all pre-formulation studies, including the following:
- Formulation records, including ingredient selection and quantities
- Physical testing results, such as viscosity, pH, and spreadability
- Stability and compatibility test results
- Observations and any adjustments made to the formulation
Prepare a Pre-formulation Study Report (Annexure-1) that includes all the findings and decisions made during the study. This report should be reviewed and approved by the QA team before proceeding to the next stage of product development.

5.7 Approval and Transition to Product Development

Once the pre-formulation studies are complete and the cream formulation is deemed stable, effective, and compliant with specifications, it can proceed to the next stage of product development, including large-scale production or clinical trials (if applicable).
Ensure that all pre-formulation study data and documentation are stored and easily accessible for future reference and regulatory inspections.

6. Abbreviations

QC: Quality Control
QA: Quality Assurance
GMP: Good Manufacturing Practices
API: Active Pharmaceutical Ingredient
cP: Centipoise (Unit of Viscosity)

7. Documents

Pre-formulation Study Report (Annexure-1)
Formulation Development Log (Annexure-2)
Stability Testing Log (Annexure-3)

8. References

Good Manufacturing Practices (GMP) Guidelines – 21 CFR Part 211
International Conference on Harmonisation (ICH) Q7 – Good Manufacturing Practice for Active Pharmaceutical Ingredients
FDA Guidelines for Pharmaceutical Product 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: Pre-formulation Study Report

Formulation Name	Batch Number	Ingredients	Test Results	Observations
Moisturizing Cream	12345	Water, Glycerin, Hyaluronic Acid	Pass (Viscosity: 4500 cP, pH: 5.5)	Stable after 6 months, no separation

Annexure-2: Formulation Development Log

Formulation Name	Batch Number	Ingredients	Process Parameters
Moisturizing Cream	67890	Water, Glycerin, Hyaluronic Acid	Mixing: 30 min, Temperature: 65°C

Annexure-3: Stability Testing Log

Test Type	Test Date	Stability Observations	Approval Status
Accelerated Stability	12/08/2025	No separation, no color change	Approved

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
01/03/2024	1.0	Initial Version	New SOP Creation	QA Head
01/03/2025	2.0	Format Revision and Updates	Standardization of Document	QA Head