Formulation and evaluation of a mucoadhesive buccal drug delivery system of Atomoxetine hydrochloride for improved bioavailability
Keywords:
Atomoxetine Hydrochloride, Buccal Film, Mucoadhesion, Controlled Release, Ion-Exchange Resin, BioavailabilityAbstract
Atomoxetine Hydrochloride (ATX HCl), a selective norepinephrine reuptake inhibitor (SNRI), suffers from low oral bioavailability due to extensive hepatic first-pass metabolism and bitter taste, limiting compliance in pediatric ADHD patients. The present study aimed to formulate and evaluate a mucoadhesive buccal drug delivery system of ATX HCl to overcome these limitations. Preformulation studies established physicochemical compatibility between the drug and selected polymers (HPMC K15M, Carbopol 934P, PVP K30). A drug–resin complex (DRC) utilizing Tulsion 339 (1:2 ratio) was prepared for taste masking. Buccal films were fabricated using the solvent casting method and optimized through systematic variation of polymer and plasticizer ratios. The optimized formulation (F3) exhibited excellent mechanical properties, neutral surface pH, satisfactory mucoadhesive strength (17.8 g), and sustained drug release (91% in 6 h), following Higuchi kinetics (R² = 0.994) with non-Fickian diffusion (n = 0.62). Ex vivo permeation across porcine buccal mucosa confirmed 82% permeation within 6 h. Analytical methods (UV at 272 nm and HPLC at t_r = 3.9 minutes) were validated as per ICH Q2(R2). Accelerated stability studies revealed no significant changes in drug content, appearance, or release profile over 6 months. The findings demonstrate that the developed mucoadhesive buccal film offers a promising alternative to conventional oral therapy by enhancing bioavailability, controlling release, masking bitterness, and improving patient compliance.
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