Broadband Diffusing Wave Spectroscopy Reveals Microstructuring of Polymer–Drug System

Abstract

Microstructuring during a phase transition and crystallization, in particular, is critical for the physicochemical properties of polymeric drug carriers and of the final dosage form. Extensive research has been dedicated to studying polymeric matrices in drug delivery, and despite substantial progress, there are still unmet challenges such as noninvasive mechanical analysis because classical rheological methods typically disturb the samples, in particular, during a phase transition. This article employs diffusing wave spectroscopy (DWS) over a broad frequency band to study polymer−drug systems in a noninvasive way. Eutectic mixtures of polyethylene glycol were investigated using two model drugs. Whereas fenofibrate barely interacted with the polymer, flurbiprofen provided a compound showing distinct molecular interactions with the carrier. Mechanical spectra were obtained during cooling of the molten polymer−drug systems. In conclusion, broadband DWS provided a better mechanistic understanding of the polymer−drug interactions and of macromolecular structuring during cooling of the eutectic melts. Such findings are relevant for a rationale design of pharmaceutical formulations during development, and such knowledge would be also important for manufacturing to achieve drug products with reproducible quality characteristics.