Principal Scientist Hikma Pharmaceuticals Usa Inc. Solon, Ohio
Particle size distribution (PSD) is a critical physicochemical attribute influencing the performance, stability, and manufacturability of drug products, especially poorly water‑soluble molecules. Micronization and nanosuspension technologies enhance dissolution and bioavailability by increasing surface area, but these benefits rely on achieving and maintaining a consistent PSD across development and scale‑up. This work outlines analytical strategies and performance linkages for micron‑ and nano‑scale particles. Laser diffraction (LD) served as the primary method for volume‑based PSD assessment of micronized APIs, generating robust Dv10, Dv50, Dv90, and Dv99 metrics. Dynamic light scattering (DLS) was applied for nanosuspension sizing, supported by microscopy (optical, SEM, cryo‑TEM) to evaluate morphology and aggregation. Additional attributes—zeta potential, crystallinity (XRPD/DSC), and dissolution—were examined to understand PSD‑performance relationships. Narrow, well‑controlled PSDs yielded improved dissolution and stability, while broader distributions promoted instability and inconsistent release. This work provides an integrated framework for PSD control supporting formulation design and scale‑up robustness.
Learning Objectives:
Upon completion, participants will be able to demonstrate an understanding of PSD method selection, interpretation of Dv10/Dv50/Dv90 metrics, and their relevance to CMC development.
