Abstract
Biopharmaceutics Classified drugs in the category II, III and IV encounter many challenges during development of buccal formulations with adequate bioavailability. This study took the advantage of nanoparticles based on permeability enhancers (PEs) to develop novel paclitaxel (PX) nanoparticles suitable for designing buccal tablets (BTs). Various PX-nanosuspensions were produced using selected PEs, then converted into dry-nanoparticles (PXNPs) using Lyophilization. Dependent variables included homogenization speed, homogenization time, and PE concentration which were optimized for appropriate particle size and entrapping efficiency. Optimized buccal tablets were then evaluated for in-vitro disintegration-time (Dt), dissolution, ex-vivo permeation, and in-vivo bioavailability using rabbit models. The results were compared to pure PX powder. The Optimized formulation containing Pluronic F68 increased PX dissolution-rate (95% after 5min) and enhanced its transport through the buccal mucosal-membrane by two folds. This formulation also showed lowest PX particle size (approximate to 250 nm). PXNPs-based tablets containing mannitol as diluents, Avicel-PH102 as a binder, and Ac-Di-Sol as super-disintegrant demonstrate short in-vitro disintegration (Dt approximate to 36sec), and rapid release rate >70% within first minute. Moreover, PX bioavailability increased six times compared to pure PX. These findings confirm that nanoparticles featured with permeability enhancers could be an effective solution for improving buccal permeability and absorption of poorly soluble chemotherapeutic drugs intended for oral tumors.