Formulation and in-vitro in-vivo characterization of buccoadhesive bilayer tablets of Carvedilol

Abstract

An effort has been made to formulate buccoadhesive bilayered tablets comprising of Carvedilol containing bioadhesive layer and drug free backing layer to release the Carvedilol for extended period of time with reduction in dosing frequency. The buccoadhesive bilayer tablets of Carvedilol were prepared by most convenient direct compression method using various proportions of Bioadhesive polymers like HPMC K 100, SCMC, PVP K 30 and CP 934 in combination with EC as an impermeable baking layer provide unidirectional drug release towards the buccal mucosa. The drug-­polymer interactions study through FTIR shows there is no significant reaction between the drug and polymer. The powder substances of drug and other excipients used for the formulation of Carvedilol buccal tablets were evaluated for derived and flow properties include bulk density, tapped density, angle of repose, Carr’s index and Hausner’s ratio before carry out the formulations. The prepared buccosdhesive bilayered tablets  were  evaluated  for  physicochemical  characteristics,  surface  pH,  swelling  index, ex-­vivo buccoadhesive strength, in-­vitro, in-vivo drug release and ex-­vivo permeation  studies.  The  noticeable  differences  in  the  results were shown to be based on characteristics and combination of bioadhesive polymers used. Stability was performed in natural human saliva and accelerated temperatures showed no significant changes in physical appearance, drug content and buccoadhesive strength. Ex-­vivo muco irritation by histological examination indicates the formulation should not cause any irritation and inflammation over the administration site. Amongst all formulation, the formulation C5 contains HPMC 25 mg, CP 12.5 mg, and PVP 12.5 mg was the best one in all the aspects. Good correlation was observed between in-­vitro and in-­vivo drug release profile of best formulation with correlation  coefficient  of  0.996,  which  reveals  the  ability  of  the  formulation  to  reproduce  the  in-­vitro  release  pattern through the biological membrane. The formulation was stable and non-­significant from p-­value obtained by one way ANOVA followed by Tukeys test.