In-vitro/In-vivo Evaluation of Paclitaxel Freeze-Dried Micellar Nanoparticles Intended for Buccal Delivery

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 (PX-NPs) using Lyophilization.

Highlights

Pluronic-based lyophilized nano-suspensions in the form of buccal tablets.

Batches of Paclitaxel nanosuspensions were prepared using bottom-up technique.

Time required for the dye solution to appear on the upper tablet surface was recorded as the wetting time.

The slope of the graph was used to calculate the permeability coefficient.

Enhancement of permeation through membrane destruction mechanism.

Enhanced drug permeability through the buccal mucosa from PF68-based nano formula.

Significant increases in half-life (p < 0.05) could be attributed to the long circulating nanoparticles and avoidance of first-pass hepatic metabolism.

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 (≈250nm).

PX-NPs-based tablets containing mannitol as diluents, Avicel-PH102 as a binder, and Ac-Di-Sol as super-disintegrant demonstrate short in-vitro disintegration (Dt≈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.

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Article information: Ahmed Mahmoud Abdelhaleem Ali, Hadel A. Abo El-Enin. Journal of Drug Delivery Science and Technology, 2021. https://doi.org/10.1016/j.jddst.2021.102424.