Novel development of Poly(2-ethyl-2-oxazoline)-based mucoadhesive buccal film for poorly water-soluble drug delivery via hot-melt extrusion.

The first-pass effect and low water solubility are crucial limitations that hinder the drug from being absorbed into the systemic circulation, followed by oral administration. The mucoadhesive buccal delivery system offers direct drug absorption through the mucosa, reaching systemic circulation and bypassing the hepatic first-pass metabolism. This approach ensures high bioavailability and overcomes the swallowing difficulties associated with traditional oral delivery systems. Here, we developed mucoadhesive buccal films for oral delivery of poorly water-soluble drugs using hot-melt extrusion (HME). Poly(2-ethyl-2-oxazoline) (PEtOx), a potential pharmaceutical excipient with high biocompatibility and versatility, was used as the primary matrix for solubility enhancement. Fenofibrate (FB), a typical Biopharmaceutics Classification System (BCS) class II drug with virtually insolubility in water, was used as the model drug. Hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), and polyethylene oxide (PEO) were combined with PEtOx to adjust the mucoadhesive property. The prepared films were in vitro characterized to delineate the impact of key formulation factors on the mechanical properties, bioadhesion, and solubility enhancement effect. We demonstrated that the complexation of PEtOx with 20% PEO (F8) resulted in over 95% drug release within 2 h, representing an over 5-fold enhancement in solubility compared to the free drug. This F8 formulation exhibited significant bioadhesion among the other formulations, with a 2.2- to 2.7-fold increase in Peak Force (PAF) and work of adhesion (WAD) relative to the control group. This study investigates HME as a continuous fabrication process for developing PEtOx-based buccal film, demonstrating a potential bioadhesive drug delivery system with a solubility improvement effect.