Investigating the Potential of Poly(2-ethyl-2-oxazoline) and Its Polymer Blends for Enhancing Fenofibrate Amorphous Solid Dispersion Dissolution Profile.

Abstract

<b>Background/Objectives:</b> This study aimed to develop a novel amorphous solid dispersion (ASD) platform using poly(2-ethyl-2-oxazoline) (PEtOx) for the solubility enhancement of poorly water-soluble drugs. Fenofibrate (FB), a Biopharmaceutics Classification System (BCS) Class II drug, was selected as the model drug. The novelty of this work lies in the formulation of dual-matrix systems by blending PEtOx of varying molecular weights (50 kDa, 200 kDa, 500 kDa) with solubility-enhancing polymers, Soluplus^® and Kollidon^® VA64, to investigate component compatibility, synergistic solubility enhancement, and the influence of PEtOx molecular weight on drug release. <b>Methods</b>: ASDs were prepared via hot-melt extrusion (HME) and characterized using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and Fourier transform-infrared spectroscopy (FTIR) to confirm FB amorphization and evaluate drug-polymer interactions. In vitro dissolution testing was performed to assess drug release performance, and stability studies were conducted at ambient conditions for one month to evaluate physical stability. <b>Results:</b> DSC, PXRD, and FTIR confirmed the successful amorphization of FB and good miscibility between PEtOx and the selected excipients. In vitro dissolution studies showed an 8-12-fold increase in FB release from ASDs compared to crystalline drug. Lower-molecular-weight PEtOx grades yielded faster release profiles, while binary blends with Soluplus^® or Kollidon^® VA64 enabled tailored drug release. Stability testing indicated that all formulations maintained their amorphous state over one month. <b>Conclusions</b>: PEtOx-based ASDs represent a versatile platform for enhancing the solubility and dissolution of poorly water-soluble drugs. By adjusting polymer molecular weight and combining with complementary excipients, release profiles can be optimized to achieve improved performance and stability.