Improvement of Dissolution Rate of Tacrolimus by Solid Dispersion Technique

Abstract

Tacrolimus has a poor solubility in water ranging from 4 to 12 μg mL−1. The mean bioavailability is ~21 %.The present study was carried out with a view to enhance the dissolution rate of poorly water-soluble drug tacrolimus using Gelucire 44/14® and Gelucire 50/13® as carriers and lactose monohydrate as an adsorbent. A combination of melt and adsorption techniques was employed for the preparation of solid dispersions (SD) to make final product easy for handling. Phase solubility study was conducted to evaluate the effect of carriers on aqueous solubility of tacrolimus. In order to elucidate the mechanism of dissolution enhancement, solid state characteristics were investigated using Fourier transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer–Peppas model and the drug release kinetics primarily as Fickian/anomalous diffusion. All prepared solid dispersions showed dissolution improvement compared to pure drug, with Gelucire 50/13® as the superior carrier over Gelucire 44/14®. Almost similar dissolution profile was obtained as a function of storage time; this can be explained by no change in XRD and DSC pattern after 45 days storage period.