A Quality by Design Approach for Particle Size Analysis of an Active Pharmaceutical Ingredient

摘要

Within the pharmaceutical industry, the particle size distribution (PSD) of an active pharmaceutical ingredient (API) may have a significant impact on both the manufacturability (flowability, packing properties, mixing, etc.) and quality attributes of the drug product (dissolution rate, bioavailability, content uniformity, etc.) [1, 2]. Throughout drug development, it is important to understand how particle size of an API impacts drug product performance and manufacturability; therefore; an appropriate analytical method is required for obtaining quantitative information on particle size distribution. Several techniques are available for particle size analysis, each with their own advantages and disadvantages; commonly used techniques for pharmaceutical include laser diffraction, dynamic light scattering, light obscuration, electrical zone sensing, sedimentation, sieve analysis, optical microscopy, and scanning electron microscopy [1,3-4], Laser diffraction is one of the more common techniques for analyzing the particle size distribution of an API [3, 5]. One drawback of laser diffraction is that this technique may not provide accurate information on the "true size" of irregularly shaped particles [6]. However, the results of laser diffraction are considered reliable for batch-to-batch monitoring for quality control purposes [6]. The significant benefits of particle size analysis by laser diffraction are the short analysis time, repeatability, reproducibility, robustness, wide measurement range, and variety of compatible sample types (dry powders, emulsions, suspensions, sprays and aerosols) [3, 4]. To ensure a robust method is utilized for particle size characterization by laser diffraction, the principles of Quality by Design (QbD) can be applied to analytical method development.