Development and Statistical Optimization of Buccoadhesive Films of Amiloride Hydrochloride: In-vitro and Ex-vivo Evaluation

The aim of present investigation was to develop an optimized buccoadhesive film of Amiloride hydrochloride (AMHCl), a BCS class III drug, to provide unidirectional sustained drug delivery to the buccal mucosa that has potential to enhance the bioavailability. The films were prepared using HPMC K4M as film former, carbopol 934P as buccoadhesive polymer and dimethyl sulfoxide as penetration enhancer, by solvent casting technique. The films were characterized for various pharmacotechnical parameters and 2³ full factorial design was employed to study the effect of independent variables. The design was validated by extra design checkpoint formulation (F9). The responses of design were analyzed using Design Expert 8.0.2 and the analytical tools of software were used to draw Pareto charts. On the basis of software analysis, formulation F4 with desirability factor of 0.698 was selected as optimized formulation and was evaluated for independent parameters. Optimized formulation showed 8.3 hr ex-vivo residence time, good permeation (41.52%) through goat buccal mucosa and 85.15% drug release after 8hr. The release kinetics of optimized formulation best fitted the higuchi model. Histopathological studies revealed no buccal mucosal damage. Hence F4 formulation can be concluded as promising drug delivery system to enhance the permeability limited absorption of AMHCl.