Pharmacokinetic Exploration of Sublingual Route for the Enhanced Bioavailability of Tacrolimus with Rabbit as Animal Model

Abstract

Introduction: The study aimed to assess the bioavailability of two sublingual formulations i.e., fast-dissolving films and tablets of the poorly bioavailable immunosuppressant drug, tacrolimus, and to compare with its marketed oral capsule formulation.Materials and Methods: Optimized film and tablet formulations of tacrolimus for sublingual administration were developed. Stability studies were performed at room temperature as well as at 40±2°C/75±2% relative humidity for 6 months. The in vivo pharmacokinetic studies were performed with rabbits as the animal model. Different pharmacokinetic parameters like tmax, Cmax, AUC, t1/2 and Ke were established and they were analyzed statistically by the student t-test.Results: The stability analysis showed a satisfactory stability profile of all the dosage forms in a six-month study. The in vivo study of the developed formulations showed better pharmacokinetic performance when compared with the marketed oral formulation. There was approximately a 2 and 1.8-fold increase in the relative bioavailability of the film and the tablet formulations respectively.Conclusion: The development of tacrolimus into sublingual dosage forms could improve the in vivo performance of the drug candidate.

Keywords: Tacrolimus; Sublingual; Bioavailability; Rabbit