Comprimidos mucoadherentes bicapa para la administración bucal de carvedilol: estudios in vitro e in vivo

Mucoadhesive bilayered system of carvedilol was designed for buccal application with the objective of improving bioavailabilityand producing sustained release. Carbopol 934P and hydroxypropylmethylcellulose K4M were employed ascarriers and the developed formulations were subjected for evaluation of surface pH, swelling index, in vitro bioadhesionand in vitro drug release studies. In vitro drug release data was analyzed for release kinetics by fi tting into Zeroorder, First order, Higuchi, Hixson-Crowell and Korsmeyer Peppas models. In vivo pharmacokinetic performance of theoptimized batch was investigated in rabbits. Data emerged from optimization and evaluation of the system revealed thatformulations exhibited satisfactory technological parameters and swelling indices. Formulation F5 showed maximumbioadhesion (3.5 ± 0.6 N) and was found to be retained for 7 h on porcine buccal mucosa. The model fi tting of invitro release data demonstrated that it followed zero order release pattern with non-fi ckian release behavior i.e. n valuesranging from 0.71 to 1.17, indicating the release was combination of tablet erosion and diffusion from the matrix.The obtained pharmacokinetic values showed signifi cant difference between Cmax, Tmax and area under curve values oforal and buccal formulation, i.e. increase in bioavailability of buccal tablet as compared with oral formulation. Plasmaconcentration curves for the buccal tablet clearly showed evidence of sustained release behavior.