Formulation and Evaluation of Mucoadhesive Buccal Films of Propafenone HCl

Abstract

Buccal drug delivery is the most suited route for local as well as systemic delivery of drugs. Conventional tablet (150mg) Propafenone HCl (PP) is available in market is used three times a day for effective treatment of supraventricular tachyarrhythmiasis. The oral absorption of Propafenone HCl is dose highly variable, with short biological half life 1.0 hr and has high first-pass metabolism leading to low bioavailability. Decrease in frequency of high dose drug via buccal drug release. There is a need to formulate mucoadhesive buccal film of PP that promotes systemic delivery, bypass of hepatic first pass metabolism and improved bioavailability and reduce the repeated administration. PP buccal films were prepared by a solvent-casting technique using various concentrations of mucoadhesive-polymers such as Hydroxyl propyl methyl cellulose (HPMC) K4M, K15M and K100M as film forming as well as rate retarding polymer with different combinations of mucoadhesive polymers like Sodium CMC, Hydroxy Propyl Cellulose (HPC), propylene glycol (PG) was selected as plasticizer and ethyl-cellulose as backing-layer, which acts like a patch providing unidirectional drug release. Prepared films were evaluated for their weight variation, thickness, surface-pH, swelling-index, and drug content uniformity, in vitro residence time, folding endurance, tensile strength and in vitro release and permeability studies. The Fourier Transform Infra-Red (FTIR) spectra and DSC thermogram showed no interaction, and Physico-chemical characteristics were found within the limit. All the developed buccal films exhibited optimal physico mechanical and pharmaceutical characteristics. From the in vitro drug release studies, this study concluded that the buccal film was successfully formulated by using a combination of HPMC K100M and HPC with the potential drug retardant characteristics compared with the polymers HPMCK4M and HPMCK15M by increasing its contact time and controlling the release. The optimized formulation followed zero order kinetics. The formulation of PP mucoadhesive buccal film was found to be satisfactory and reasonable. The in vivo pharmacokinetic study was conducted in healthy rabbits and it was observed from the results that the oral bioavailability of optimized formulation (PP18) was increased significantly when compared to the marketed formulations. Relative bioavailability with respect to marketed formulation (Rythmol) was found to be 124.9. The increased bioavailability may be due to the mucoadhesive mechanism of dosage form in buccal area for longer duration.