consistency.

2. Scope

This SOP applies to Analytical Method Development (AMD) personnel engaged in characterizing spray-based pharmaceutical products using laser diffraction or cascade impaction techniques to determine droplet size parameters.

3. Responsibilities

• Analytical Scientist: Performs method development, calibration, and routine analysis of droplet size using validated equipment.
• QC Analyst: Verifies system suitability and performs replicate testing.
• QA Executive: Reviews validation reports and authorizes use of method for regulatory submission or batch release testing.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring the accuracy, reproducibility, and regulatory compliance of the droplet size distribution method.

5. Procedure

5.1 Instrumentation and Calibration

1. Use validated laser diffraction systems (e.g., Malvern Spraytec) or cascade impactors (e.g., NGI, Andersen) as per product type.
2. Calibrate laser diffraction analyzer using traceable polystyrene latex beads.
3. Verify stage cut-off diameters in impactors before use.

5.2 Sample Preparation

1. Use 3 test units per batch (e.g., nasal sprays or MDIs).
2. Shake the canister or bottle as per product label prior to actuation.
3. Use a standard actuation force and interval (e.g., 3 actuations at 30-second intervals).

5.3 Test Conditions

1. Ambient conditions: 20–25°C, 45–55% RH unless otherwise specified.
2. Spray through a fixed distance to detector (e.g., 5 cm from nozzle tip).

5.4 Measurement and Data Analysis

1. Record volume-based distribution using software-provided particle sizing module.
2. Calculate:
   • Dv10: Diameter below which 10% of volume exists
   • Dv50 (Median): Droplet size below which 50% of volume exists
   • Dv90: Diameter below which 90% of volume exists
   • Span = (Dv90 – Dv10)/Dv50

5.5 Acceptance Criteria

1. Median droplet size (Dv50): Typically 30–100 µm for nasal sprays (product-specific).
2. Span value should be ≤ 1.5 unless justified.
3. % RSD of replicate measurements ≤ 10%.

5.6 Method Validation

1. Validate for:
   • Repeatability (n = 6 sprays, % RSD)
   • Robustness (variation in actuation force/distance)
   • Specificity (no interference from propellant or container)

5.7 Documentation

1. Maintain raw data, instrument logs, calibration certificates, and software output files.
2. Include graphical representation of particle size distribution curve in the report.

6. Abbreviations

• Dv10/Dv50/Dv90: Droplet diameter at 10%, 50%, and 90% cumulative volume
• RSD: Relative Standard Deviation
• NGI: Next Generation Impactor
• MDI: Metered Dose Inhaler

7. Documents

1. Spray Droplet Size Data Log – Annexure-1
2. Calibration Certificate Log – Annexure-2
3. Droplet Size Validation Report – Annexure-3

8. References

• FDA Guidance: Nasal Spray and Inhalation Solution Product Quality
• USP <601>: Aerosols, Nasal Sprays, Metered-Dose Inhalers
• ISO 13320: Particle Size Analysis by Laser Diffraction

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Ashwini Jadhav	Rohit Bansal	Sunita Reddy
Designation	Analytical Scientist	QA Reviewer	Head – AMD
Department	Analytical Method Development	QA	Analytical Method Development

11. Annexures

Annexure-1: Spray Droplet Size Data Log

Batch No.	Device ID	Dv10 (µm)	Dv50 (µm)	Dv90 (µm)	Span	% RSD
NS-025	NAS-03	18	52	108	1.73	8.2

Annexure-2: Calibration Certificate Log

Instrument ID	Calibration Date	Certified By	Next Due Date
LD-1001	01/05/2025	IQAC	01/05/2026

Annexure-3: Droplet Size Validation Report

Laser diffraction-based droplet size method validated for nasal spray formulation. Dv50 ranged between 48–54 µm with Span ≤ 1.5. Method found to be repeatable and robust for routine use.

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
21/05/2025	2.0	Added span calculations and ISO references	Annual Review and Compliance Update	Sunita Reddy
02/05/2022	1.0	Initial SOP Release	New SOP	QA Head