Scope

This SOP applies to Analytical Method Development personnel engaged in characterizing the particle size of active or excipient phases in lotion-based formulations during formulation development, validation, and stability studies.

3. Responsibilities

• Analytical Scientist: Performs sample dispersion and operates particle size analyzer or microscope.
• QC Analyst: Assists in sample handling and record keeping.
• QA Executive: Verifies data integrity and ensures compliance with method validation requirements.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring correct method validation, equipment calibration, and scientific justification of particle size characterization techniques.

5. Procedure

5.1 Instrumentation Options

1. Laser Diffraction Particle Size Analyzer (e.g., Malvern Mastersizer)
2. Optical/Polarized Light Microscope (with calibrated micrometer scale)

5.2 Sample Preparation

1. Ensure the lotion sample is homogenous.
2. For laser diffraction: Disperse 1–2 mL of lotion in 20–50 mL of suitable dispersant (e.g., purified water or isopropanol) using a sonicator for 2 minutes.
3. For microscopy: Place a drop of lotion or dispersion on a clean glass slide and cover with a coverslip.

5.3 Instrument Setup and Calibration

1. Calibrate the particle size analyzer with a certified standard before use (Annexure-2).
2. Set measurement parameters including obscuration, refractive index, and dispersant properties.

5.4 Measurement by Laser Diffraction

1. Transfer the dispersion into the analyzer’s sample cell.
2. Initiate measurement and acquire at least 3 scans per sample.
3. Record d(10), d(50), and d(90) values.
4. Clean the system thoroughly after use.

5.5 Measurement by Microscopy (Alternative)

1. Observe the slide under 400x magnification.
2. Measure at least 100 particles using an eyepiece micrometer.
3. Calculate mean particle diameter and range.

5.6 Acceptance Criteria

• d(50) value typically between 1 µm to 10 µm depending on formulation type
• RSD for triplicate measurements ≤ 5%
• No visible aggregation or bimodal distribution

5.7 Validation Parameters

1. Precision: Repeatability and intermediate precision studies (RSD ≤ 5%)
2. Accuracy: Verified using certified particle size standards
3. Robustness: Studied by varying sonication time and dispersant type

6. Abbreviations

• RSD: Relative Standard Deviation
• d(50): Median Particle Diameter
• QA: Quality Assurance
• AMD: Analytical Method Development

7. Documents

1. Particle Size Test Log – Annexure-1
2. Instrument Calibration Certificate – Annexure-2
3. Validation Report Summary – Annexure-3

8. References

• USP <429>: Light Diffraction Measurement of Particle Size
• ICH Q2(R1): Validation of Analytical Procedures
• Ph. Eur. 2.9.31: Particle Size Distribution

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Rahul Patankar	Meera Desai	Sunita Reddy
Designation	Analytical Scientist	QA Reviewer	Head – AMD
Department	Analytical Method Development	QA	Analytical Method Development

11. Annexures

Annexure-1: Particle Size Test Log

Sample ID	d(10)	d(50)	d(90)	Status
LTN-261-01	1.5 µm	3.2 µm	6.4 µm	Pass

Annexure-2: Instrument Calibration Certificate

Calibration Date	Standard Used	Expected (µm)	Observed (µm)	Status
15/05/2025	Polystyrene Latex	5.00	4.95	Pass

Annexure-3: Validation Report Summary

Particle size method validated for lotion formulation LTN-261. Repeatability (RSD = 2.1%), accuracy with certified standard (98.5%), and robustness across dispersant types confirmed. Method found suitable for routine product monitoring and release.

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
21/05/2025	2.0	Added microscopy method as alternate option	Annual SOP Review	Sunita Reddy
01/05/2022	1.0	Initial SOP Release	New SOP	QA Head