In Vitro/In Vivo Evaluation and Bioavailability Study of Amitriptyline Hydrochloride from the Optimized Oral Fast Dissolving Films

Abstract

The present investigation was undertaken with the objective of developing fast dissolving film(s) of a tricyclic antidepressant drug amitriptyline hydrochloride in order to improve its bioavailability, optimize its therapeutic action especially when used to treat major depression and to enhance the compliance for the developmentally disable, mentally ill, elderly and pediatric patients. Fast dissolving dosage forms have acquired great importance in pharmaceutical industry because of their unique properties. Ten formulations were prepared by solvent casting method using different polymer types, plasticizer types, surfactant concentrations and different ratio of hydroxypropyl methyl cellulose and maltodextrin. The prepared films were evaluated for folding endurance, thickness, drug content, in vitro/in vivo disintegration time, drug release and tensile test. The optimized formula F8 containing  HPMC 15cp and maltodextrin in 1:1 ratio showed minimum in vitro/in vivo disintegration time 16.8, 13.2 seconds respectively, highest dissolution rate i.e. T80% 1.1 minutes,  D2 min (%) 89.77% and satisfactory mechanical properties. The optimized film was further evaluated for bioavailability compared with a marketed solution (Amitriptyline Hydrochloride®), the study based on cross over design using experimental animals (rabbits). The pharmacokinetic results revealed that the fast dissolving films has higher peak blood concentration (Cmax, 0.927µg/ml) within shorter time (Tmax, 2 hours), indicating rapid absorption and faster onset of action with acceptable bioavailability value. These findings suggest that the fast dissolving film containing amitriptyline hydrochloride is expected to become one of choices for the treatment of acute depression.