Design and In vivo Evaluation of Buccoadhesive Hydrophilic Polymer Matrix Films of Losartan Potassium

Introduction: The buccal mucosal route can be considered as an alternative to oral administration for the purpose of improving bioavailability and therapeutic efficacy of drugs such as losartan potassium that suffers from significant first pass metabolism. Objectives: The objective of this investigation was to formulate mucoadhesive buccal films of losartan potassium, an antihypertensive and evaluate them for in vitro drug release and in vivo buccal absorption. Methods: Film formulations were prepared from the hydrophilic polymers, hydroxy propylmethyl cellulose/sodium carboxymethyl cellulose and carbopol 934 P with suitable plasticizers. They were then subjected to studies for evaluating physical and mechanical properties as well as in vitro and in vivo drug release in rabbits. Results: Formulations containing higher proportions of the cellulose polymers exhibited faster rate of swelling. Faster swelling due to rapid rehydration and greater bioadhesive strength was produced by the sodium carboxymethyl cellulose films in comparison to those of hydroxyl propylmethyl cellulose. Kinetic analysis of in vitro drug release data indicated first order release from all formulations and application of Peppas equation indicated non-fickian diffusion for most formulations. Plasma level studies in rabbits revealed that the calculated values of the pharmacokinetic parameters Cmax , Tmax and AUC in the groups that received the optimized formulations were statistically different (P<0.005) from that of the groups that received the oral solution at the same dosage level. The differences in these parameters between F1 and F4 were however, not statistically significant. Conclusion: In vivo studies have confirmed the efficacy of the buccal route in improving the systemic bioavailability of losartan potassium from mucoadhesive films. F1 and F4 can be considered as promising formulations for clinical application.