Industry White Paper: Contemporary Opportunities and Challenges in Characterizing Crystallinity in Amorphous Solid Dispersions

Abstract

Members of the IQ Consortium ″Working Group on Characterization on Amorphous Solid Dispersions″ shares here a perspective on the analytical challenges, and limitations of detecting low levels of crystalline drug substance in amorphous solid dispersions (ASDs) and associated drug products. These companies aim to employ highly sensitive commercially available analytical technologies to guide development, support control strategies, and enable registration of quality products. We hope to promote consistency in development and registration approaches and guide the industry in development of "characterization best practices" in the interest of providing high quality products for patients. The first half of this perspective highlights the unique challenges of analytical methodologies to monitor crystalline drug substance in ASDs and their associated drug products. Challenges around use of limit tests, analyte spiking experiments, and method robustness are also underscored. The latter half describes the merits and limitations of the diverse analytical "toolbox" (such as XRPD, NIR and DSC), which can be readily applied during development and, in some cases, considered for potential application and validation in the commercial QC setting when necessary.

Keywords: Amorphous solid dispersion(s) (ASD); Analysis; Crystallinity; Differential scanning calorimetry (DSC); Infrared (IR) spectroscopy; Near-infrared spectroscopy (NIRS); Raman spectroscopy; Solid-state NMR (SSNMR) spectroscopy; X-ray powder diffraction (XRD).