Continuous Processing Strategies for Amorphous Solid Dispersions of Itraconazole: Impact of Polymer Selection and...

Background: The limited aqueous solubility of BCS Class II drugs, exemplified by itraconazole (ITR), continues to hinder their bioavailability and therapeutic performance following oral administration. The present study investigated the development of amorphous solid dispersions (ASDs) of ITR via continuous manufacturing technologies, such as hot melt extrusion (HME) and spray drying (SD), to improve drug release. Methods: Polymer selection was guided by Hansen solubility parameter (HSP) analysis, film casting, and molecular modeling, leading to the identification of aminoalkyl methacrylate copolymer type A (Eudragit^® EPO), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus^®), and hypromellose acetate succinate HG (AQOAT^® AS-HG) as suitable carriers. ASDs were prepared at drug-to-polymer ratios of 1:1, 1:2, and 2:1. Comprehensive characterization was performed using ATR-FTIR, NMR, DSC, PXRD, SEM, PLM, and contact angle analysis. Results: HME demonstrated higher process efficiency, solvent-free operation, and superior dissolution enhancement compared to SD. Optimized HME-based ASDs were formulated into tablets. The ITR-Eudragit^® EPO formulation achieved 95.88% drug release within 2 h (Weibull model, R² > 0.99), while Soluplus^® and AQOAT^® AS-HG systems achieved complete release, best described by the Peppas-Sahlin model. Molecular modeling confirmed favorable drug-polymer interactions, correlating with the formation of stable complex and enhanced release performance. Conclusions: HME-based continuous manufacturing provides a scalable and robust strategy for improving the oral delivery of poorly water-soluble drugs. Integrating predictive modeling with experimental screening enables the rational design of ASD formulations with optimized dissolution behavior, offering potential for improved therapeutic outcomes in BCS Class II drug delivery.