Eliminating Gastrointestinal Barriers in Parkinson’s Therapy: DoE-Optimized Pramipexole Orodispersible Films with Enhanced Buccal Permeation

Abstract

The present study aimed to develop and optimize fast dissolving oro-dispersible films (ODFs) of Pramipexole HCl as a strategy to overcome gastrointestinal limitations and enhance drug availability for the management of Parkinson’s disease. A total of 27 formulations (F1–F27) were prepared using the solvent casting method and systematically optimized using a 3³ full factorial design by varying concentrations of HPMC E50, Kollidon 30, and propylene glycol. The prepared films were evaluated for physicochemical properties including thickness, tensile strength, folding endurance, drug content, surface pH, disintegration time, and in vitro drug release.

All formulations exhibited acceptable mechanical strength, uniform drug distribution (96.5–99.5%), and near-neutral surface pH, indicating suitability for buccal administration. Among all batches, formulation F24 demonstrated superior performance with minimal thickness (0.11 mm), highest folding endurance (130), rapid disintegration (9 seconds), and maximum drug content (99.5%). In vitro dissolution studies revealed a rapid drug release profile, with F24 achieving ~99% release within 30 minutes, significantly outperforming the marketed tablet, which showed slower release under identical conditions.

Ex vivo permeation studies using goat buccal mucosa further confirmed enhanced drug transport from F24, exhibiting higher cumulative permeation (92.4%) and flux compared to the marketed formulation. Drug-excipient compatibility studies (FTIR, DSC) indicated no significant interactions, while SEM analysis confirmed uniform drug distribution within the polymeric matrix. Stability studies conducted under accelerated conditions demonstrated minimal changes in physicochemical properties, confirming formulation robustness.

Overall, the optimized oro-dispersible film (F24) offers a promising alternative to conventional oral dosage forms by providing rapid onset of action, improved drug release, and enhanced buccal permeation, thereby potentially improving therapeutic efficacy in Parkinson’s disease management.