SOP for Manufacturing Nasal Powders Using Dry Powder Inhalers (DPIs)

Standard Operating Procedure for Manufacturing Nasal Powders Using Dry Powder Inhalers (DPIs)

1) Purpose

This SOP outlines the procedures for manufacturing nasal powder formulations using Dry Powder Inhalers (DPIs). These formulations ensure that powders are accurately dosed, have a consistent particle size, and are effectively delivered to the nasal cavity for therapeutic use.

2) Scope

This SOP applies to all personnel involved in the manufacturing, testing, and quality control of nasal powders utilizing DPIs at [Company Name]. The document provides guidance for powder preparation, particle size control, blending, and device filling.

3) Responsibilities

Operators: Responsible for preparing the powder formulation, blending ingredients, and ensuring proper particle size for nasal delivery.
Quality Assurance (QA): Verifies that the product meets all specifications, including uniformity, particle size, and dosing accuracy.
Maintenance Team: Ensures proper functioning and cleanliness of equipment, including the DPI filling machines.

4) Procedure

4.1 Equipment Setup

4.1.1 Inspection of Dry Powder Inhaler Filling Machine

Inspect the DPI filling machine to ensure it is clean and fully operational.
Ensure that all parts, including the powder hopper, nozzles, and dosing chambers,

are sterile and ready for use.

Record the equipment setup details in the equipment logbook.

4.1.2 Calibration of Analytical Instruments

Calibrate all instruments used for measuring particle size and dosing uniformity. These may include laser diffraction analyzers and powder dosing machines.
Document calibration results in the calibration log.

4.2 Material Preparation

4.2.1 Weighing and Blending

Weigh the active pharmaceutical ingredients (APIs) and excipients (e.g., lactose, carriers) according to the batch manufacturing record (BMR).
Mix the materials in a powder blender at the designated speed and duration, ensuring uniform distribution of the API and excipients.
After blending, sieve the powder to ensure consistent particle size distribution, with a target size of 1-5 microns for nasal delivery.

4.2.2 Powder Homogeneity Testing

Take samples from various points of the blend and test for uniformity using validated analytical methods (e.g., HPLC or UV spectrophotometry).
Record the homogeneity results in the batch records.

4.3 Powder Filling in DPI Devices

4.3.1 Filling Process

Transfer the blended powder into the DPI filling machine. Set the machine to the specified dosing quantity per inhaler (typically between 5-25 mg of powder per dose).
Check dosing accuracy by testing 10 filled DPI units. Ensure the deviation is within ±5% of the target dose.

4.3.2 Device Assembly and Packaging

After filling, assemble the DPI units by sealing the dosing chambers and attaching the DPI mouthpieces.
Package the final products in sealed containers and label them with batch numbers, expiration dates, and dosage information.

4.4 Particle Size and Moisture Content Testing

4.4.1 Particle Size Analysis

Measure the particle size distribution using a laser diffraction particle size analyzer. Ensure that the powder falls within the designated particle size range of 1-5 microns for nasal absorption.

4.4.2 Moisture Content Testing

Test the moisture content of the powder using a moisture analyzer. Ensure that the moisture content is below 5% to prevent clumping and degradation of the powder.

4.5 Microbial and Endotoxin Testing

Perform microbial testing on the final powder formulation to ensure sterility. Use standard procedures, such as plate counting or membrane filtration.
Conduct endotoxin testing to ensure the formulation meets safety requirements.
Document all microbial and endotoxin test results in the quality control log.

4.6 Stability Testing

Conduct stability testing on the nasal powder to evaluate its shelf life and ensure it maintains the required potency, particle size, and moisture content over time.
Place samples of the nasal powder in controlled environments with varying temperature and humidity conditions and test them at 1-month, 3-month, and 6-month intervals.
Document all stability test results in the stability testing log.

5) Abbreviations, if any

API: Active Pharmaceutical Ingredient
DPI: Dry Powder Inhaler
QA: Quality Assurance
BMR: Batch Manufacturing Record

6) Documents, if any

Batch Manufacturing Record (BMR)
Particle Size Analysis Log
Moisture Content Testing Log
Microbial and Endotoxin Testing Records
Stability Testing Log

7) References, if any

FDA Guidance on Nasal Powder Formulations
ICH Q8(R2) – Pharmaceutical Development Guidelines

8) SOP Version

Version 1.0

Annexure

Particle Size and Moisture Content Log Template


  
    Date
    Formulation
    Particle Size (µm)
    Moisture Content (%)
    Operator Initials
    QA Approval
  
  
    DD/MM/YYYY
    Formulation Name
    Size
    Moisture
    Operator Name
    QA Name