according to established procedures, ensuring the consistency and reproducibility of the results for quality assurance purposes.

Project Managers: Coordinate the particle size analysis process, ensuring that timelines are met and resources are appropriately allocated for formulation testing.

4) Procedure

The following steps outline the procedure for conducting particle size analysis in formulation screening:

1. Step 1: Define Formulation Requirements
   1. Identify the type of formulation to be tested (e.g., tablet, suspension, emulsion) and determine the desired particle size range based on the formulation’s intended use and therapeutic goals.
   2. Establish the particle size distribution criteria, such as the d90, d50, and d10 values, which correspond to the diameters at which 90%, 50%, and 10% of the particles are smaller, respectively.
   3. Set acceptance criteria based on regulatory guidelines (e.g., USP, EP) and the formulation’s intended application (e.g., drug release, stability, and bioavailability requirements).
2. Step 2: Sample Preparation
   1. Ensure that the sample is homogeneous and free from clumping or aggregation before conducting particle size analysis. For suspensions, emulsions, or powders, ensure that the sample is properly dispersed or suspended in an appropriate medium.
   2. If testing solid dosage forms (e.g., tablets or capsules), grind or mill the sample to obtain a powder suitable for particle size measurement.
   3. For liquid formulations, dilute the sample with a solvent if necessary to achieve the desired concentration and avoid interference with the measurements.
3. Step 3: Particle Size Analysis Method Selection
   1. Select the appropriate method for particle size analysis based on the formulation type and required sensitivity:
      • Laser Diffraction: Suitable for measuring a wide range of particle sizes, from sub-micron to millimeters, commonly used for powders and suspensions.
      • Dynamic Light Scattering (DLS): Ideal for measuring the size of nanoparticles or sub-micron particles in suspensions and emulsions.
      • Sieve Analysis: Used for coarse powders, where particle sizes are larger (e.g., granules and tablets).
   2. Ensure that the selected method provides reliable and reproducible results within the required particle size range.
4. Step 4: Conduct Particle Size Analysis
   1. Laser Diffraction:
      • Load the sample into the laser diffraction instrument, ensuring the proper dispersion or suspension in a suitable liquid medium.
      • Run the analysis according to the instrument’s operating protocol, ensuring that the laser beam is appropriately focused and the measurement settings are correctly adjusted.
      • Record the particle size distribution and report the d10, d50, and d90 values.
   2. Dynamic Light Scattering (DLS):
      • Prepare the sample in a dispersing medium (e.g., water) and load it into the DLS instrument’s cuvette.
      • Run the DLS measurement, ensuring that the system’s temperature and settings are optimal for the sample’s characteristics.
      • Record the particle size distribution and calculate the z-average size and polydispersity index (PDI) if required.
   3. Sieve Analysis:
      • Prepare the sample and load it onto a series of sieves with different mesh sizes.
      • Vibrate the sieves for a set time and collect the material retained on each sieve.
      • Weigh the material on each sieve and calculate the percentage distribution based on the weight fraction collected on each sieve.
5. Step 5: Data Collection and Analysis
   1. Record all measurement parameters (e.g., laser settings, temperature, sample dispersion) during the analysis.
   2. Analyze the data to calculate particle size distribution, including the mean particle size (d50), standard deviation, and the PDI (for DLS).
   3. Compare the particle size distribution to the established acceptance criteria and determine whether the formulation meets the required specifications.
6. Step 6: Documentation and Reporting
   1. Document all observations, measurement conditions, and results from the particle size analysis in a detailed report.
   2. Prepare a summary report that includes the formulation’s particle size distribution, any deviations from the expected results, and recommendations for further optimization if necessary.
   3. Ensure that all records are signed, dated, and stored in compliance with Good Laboratory Practices (GLP) and regulatory standards.
7. Step 7: Sample Disposal
   1. Dispose of any remaining test samples, solvents, and analytical materials according to safety protocols and environmental regulations.
   2. Ensure that hazardous materials are disposed of in designated chemical waste containers in compliance with safety guidelines.

5) Documents

The following documents should be maintained during the particle size analysis of formulations:

1. Particle Size Analysis Records
2. Measurement Parameters and Conditions
3. Data Analysis and Statistical Reports
4. Particle Size Distribution Summary Report
5. Sample Disposal Records

6) Abbreviations

• API: Active Pharmaceutical Ingredient
• GLP: Good Laboratory Practices
• HPLC: High-Performance Liquid Chromatography
• DLS: Dynamic Light Scattering
• PDI: Polydispersity Index

7) References

References to regulatory guidelines and scientific literature that support this SOP:

• FDA Guidance for Pharmaceutical Development
• USP <788> on Particulate Matter in Injections
• ICH Q8(R2) Pharmaceutical Development

8) Version

Version 1.0: Initial version of the SOP.

9) Annexure

Particle Size Analysis Results Template

Formulation ID	Method Used	d10 (µm)	d50 (µm)	d90 (µm)	Polydispersity Index (PDI)