Using Dry Dispersion Laser Diffraction to Assess Dispersibility in Spheronized Agglomerate Formulations

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Analytical Chemistry

Background:

• Accurate particle size distribution (PSD) is crucial for drug delivery and formulation performance.
• Cascade impaction is a standard but labor-intensive method for assessing aerodynamic particle size distribution (APSD).
• Laser diffraction offers a potentially faster alternative for particle size analysis.

Purpose of the Study:

• To evaluate dry dispersion laser diffraction as a surrogate for cascade impaction in characterizing agglomerate formulations.
• To identify geometric particle size metrics from laser diffraction that correlate with APSD.
• To assess the potential of laser diffraction to streamline product development.

Main Methods:

• Dry dispersion laser diffraction was employed to measure particle size distribution (PSD) of eleven agglomerate batches.
• Cascade impaction was used to determine the aerodynamic particle size distribution (APSD) for the same batches.
• Semi-empirical analysis was performed to correlate PSD and APSD metrics.

Main Results:

• A strong correlation was found between impactor-sized mass (%ISM) and cumulative PSD fraction <14.5 µm.
• The fine particle fraction (FPF) showed a high correlation (R-squared = 0.974) with the cumulative PSD fraction <0.99 µm.
• Mass median aerodynamic diameter (MMAD) did not correlate well with cumulative PSD fractions.

Conclusions:

• Laser diffraction can serve as a viable surrogate for cascade impaction in assessing agglomerate dispersibility.
• This approach offers significant savings in labor and turnaround time, facilitating efficient product development.
• Geometric particle size metrics from laser diffraction can predict key APSD parameters relevant to inhalation products.