Nanosuspension-Based Repaglinide Fast-Dissolving Buccal Film for Dissolution Enhancement.

Abstract

Drug solubility and dissolution remain a significant challenge in pharmaceutical formulations. This study aimed to formulate and evaluate repanglinide (RPG) nanosuspension-based buccal fast-dissolving films (BDFs) for dissolution enhancement. RPG nanosuspension was prepared by the antisolvent-precipitation method using multiple hydrophilic polymers, includingsoluplus®, polyvinyl alcohol, polyvinyl pyrrolidine, poloxamers, and hydroxyl propyl methyl cellulose. The nanosuspension was then directly loaded into BDFs using the solvent casting technique. Twelve formulas were prepared with a particle size range of 81.6-1389nm and PDI 0.002-1 for the different polymers. Nanosuspensions prepared with soluplus showed a favored mean particle size of 82.6 ± 3.2nm. The particles were spherical and non-aggregating, as demonstrated by SEM imaging. FTIR showed no interaction between soluplus and RPG. Faster dissolution occurred for the nanosuspension in comparison with pure RPG (complete release vs 60% within 30min). The nanosuspension was successfully incorporated into BDFs. The optimum film formula showed 28s disintegration time, and 97.3% RPG released within 10min. Ex-vivopermeation profiles revealed improved RPG nanosuspensionpermeationwith the cumulative amount of RPGpermeated is103.4% ± 10.1 and a flux of 0.00275mg/cm2/min compared to 39.3% ± 9.57 and a flux of 0.001058mg/cm2/min for pure RPG. RPG was successfully formulated intonanosuspension that boosted drug dissolution and permeation.The selection of the ultimate NP formula was driven byoptimal particlesize, distribution, and drug content. Soluplus NPs were shown to be thesuccessful formulations, which were furtherincorporated intoa buccal film. The film was evaluated for ex-vivo permeation, confirming successful RPG formulation with improved performance compared to pure drugs.