Procedure for Particle Size Analysis in Ointments
| Department | Quality Control (QC)/Quality Assurance (QA)/Analytical Development |
|---|---|
| SOP No. | SOP/Ointment/066 |
| Supersedes | V 1.0 |
| Page No. | Page X of Y |
| Issue Date | [Insert Issue Date] |
| Effective Date | [Insert Effective Date] |
| Review Date | [Insert Review Date] |
1. Purpose
The purpose of this Standard Operating Procedure (SOP) is to define the method for determining the particle size distribution of active pharmaceutical ingredients (API) and excipients in ointments. Particle size plays a crucial role in product efficacy, consistency, and stability.
2. Scope
This SOP applies to all personnel in the Quality Control (QC), Quality Assurance (QA), and Analytical Development departments responsible for conducting particle size analysis of ointments during formulation development, in-process control, and final batch release.
3. Responsibilities
- Quality Control Analyst: Conducts particle size analysis and records results.
- Quality Assurance Personnel: Reviews and approves test results.
- Production Supervisor: Ensures that ointment batches meet the particle size specifications.
- R&D and Analytical Development Team: Investigates deviations and suggests corrective actions.
4. Accountability
The QC, Analytical Development, and QA Managers are accountable for ensuring that particle size analysis is conducted accurately and documented as per regulatory and GMP standards.
5. Procedure
5.1 Equipment and Materials
- Laser Diffraction Particle Size Analyzer
- Microscope with calibrated eyepiece micrometer
- Dynamic Light Scattering (DLS) Instrument (if applicable)
- Ultrasonic bath (if dispersion is required)
- Appropriate dispersing media (e.g., purified water, isopropyl alcohol)
- Glass slides and cover slips
- Disposable pipettes
- Data recording sheets
5.2 Sample Preparation
- Weigh an appropriate quantity of the ointment sample (e.g., 0.5 g – 1 g).
- If needed, dilute the sample with an appropriate dispersing medium.
- Sonicate the sample for 5–10 minutes to ensure uniform dispersion of particles.
- For microscopy analysis, place a small drop on a glass slide and cover with a cover slip.
5.3 Particle Size Determination Methods
5.3.1 Laser Diffraction Method
- Turn on the Laser Diffraction Particle Size Analyzer and allow stabilization.
- Ensure the instrument is calibrated with a reference standard.
- Load the sample into the instrument’s dispersion unit.
- Adjust the refractive index settings according to the sample matrix.
- Run the analysis and obtain the particle size distribution report.
- Record results, including D10, D50, and D90 values.
5.3.2 Microscopy Method
- Place a small sample on a glass slide.
- Observe under a microscope at appropriate magnification (e.g., 100x or 400x).
- Measure particle size using a calibrated eyepiece micrometer.
- Record the largest and smallest observed particles.
5.3.3 Dynamic Light Scattering (DLS) Method (if applicable)
- Prepare the sample by dispersing it in a suitable liquid medium.
- Ensure the sample is free from bubbles and large aggregates.
- Load the sample into the DLS instrument and measure particle size distribution.
5.4 Acceptance Criteria
- Particle size distribution should be within the defined specification range (e.g., D90 < 50 µm).
- Deviation from specifications requires batch review and possible reprocessing.
5.5 Documentation
- Record all particle size analysis results in the Particle Size Test Log.
- Document instrument calibration details.
- QA personnel must review and approve results before batch release.
6. Abbreviations
- GMP – Good Manufacturing Practices
- QA – Quality Assurance
- QC – Quality Control
- API – Active Pharmaceutical Ingredient
- D10, D50, D90 – Particle Size Percentiles
- DLS – Dynamic Light Scattering
7. Documents
- Particle Size Test Log (Annexure-1)
- Ointment Batch Particle Size Report (Annexure-2)
8. References
- WHO GMP Guidelines for Pharmaceutical Manufacturing
- USP <429> – Light Diffraction Measurement of Particle Size
- ICH Q2 (R1) – Validation of Analytical Procedures
9. SOP Version
Version 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Particle Size Test Log
| Date | Batch Number | Sample Weight (g) | D10 (µm) | D50 (µm) | D90 (µm) | Result | Verified By |
|---|---|---|---|---|---|---|---|
| 01/02/2025 | OINT-101 | 0.5 | 5 | 15 | 45 | Pass | QA Officer |
| 02/02/2025 | OINT-102 | 0.5 | 4 | 14 | 42 | Pass | QA Officer |
Annexure-2: Ointment Batch Particle Size Report
| Date | Batch Number | Test Method | Acceptance Criteria | Result | Final Status | Approved By |
|---|---|---|---|---|---|---|
| 01/02/2025 | OINT-101 | Laser Diffraction | D90 < 50 µm | 45 µm | Approved | QA Head |
| 02/02/2025 | OINT-102 | Microscopy | D90 < 50 µm | 42 µm | Approved | QA Head |