Formulation development of sublingual films and tablets of tacrolimus for bioavailability enhancement

Abstract

newlineTacrolimus is the most successfully used immunosuppressant today for the prevention of allograft rejection The drug is classified under BCS class II with low solubility and high permeability and has shown poor pharmacokinetic properties as well as bioavailability So the aim of the study was to develop sublingual fast dissolving dosage forms ie films and tablets of tacrolimus to improve its bioavailability In the first phase of the work in order to increase the solubility of tacrolimus inclusion complexes with beta cyclodextrin were prepared by utilizing kneading method and were subjected to various in vitro evaluations The inclusion complexes showed more than fourfold increase in aqueous solubility In the second phase the optimized inclusion complexes were further developed into fast dissolving tablets by direct compression method In the third phase films were developed with inclusion complexes using solvent casting technique with HPMC E5 as film forming polymer The design and optimization of films were achieved by Design of Experiment approach using central composite design The developed tablets and films were characterized by different in vitro evaluations and they showed satisfactory performances on all evaluations The results of stability analysis revealed that the prepared formulations retained their stability under accelerated storage conditions as per ICH guidelines The optimized formulations were subjected to in vivo bioavailability studies using New Zealand white rabbits and showed enhancement in bioavailability in comparison with oral marketed formulation Thus the present study has demonstrated the successful utility of sublingual route for the administration of the life saving drug tacrolimus