IMPLEMENTING CENTRAL COMPOSITE DESIGN FOR THE DEVELOPMENT OF TACROLIMUS FILM FOR SUBLINGUAL ADMINISTRATION

Abstract

Objective: The study aimed to develop fast-dissolving films (FDFs) of the immunosuppressant drug tacrolimus monohydrate for sublingual administration, employing central composite design (CCD), to improve its bioavailability. Methods: Tacrolimus: β-cyclodextrin inclusion complexes prepared earlier were formulated into FDFs. CCD was used for developing optimal film formulation with the desired characteristics. The solvent casting method was used for the preparation of films. For optimization, the independent variables selected were the concentration of hydroxy propyl methyl cellulose E5 (HPMC E5) (X1) and concentration of croscarmellose sodium (CCS) (X2) and the responses were disintegration time (Y1) and percentage drug release at 5 min (Y2). The suggested optimal films were subjected to further characterization. Results: All the formulations showed good mechanical properties. The composition of optimized FDF constituted 3.016% w/v of HPMC and 11.731%w/w of CCS and its average disintegration time was 27.28s and showed 83.13% mean drug release at 5 min. Differential Scanning calorimetry (DSC) analysis showed complete dispersion and partial conversion into the amorphous form of the drug, which was also confirmed by X-ray diffraction (XRD) studies. Scanning Electron Microscopy (SEM) revealed the smooth and porous nature of the film. Conclusion: The developed FDF may be used sublingually for delivering tacrolimus efficiently, avoiding its oral bioavailability problems.