Development and characterization of liquid and solid self-microemulsifying drug delivery system of Tacrolimus

Abstract

Tacrolimus is an immunosuppressant agent for the prevention and treatment of graft rejection in solid organ transplantation patients. Tacrolimus is a poorly water-soluble drug. Its absorption is further limited due to the involvement of an efflux transporter P-glycoprotein and metabolism via cytochrome P450. The objective of presentinvestigation was to develop and characterize a liquid self-microemulsifying drug delivery system (SMEDDS) and a solid SMEDDS by using bioenhancer excipients like Tween 20 and Tween 80, which are known for their inhibiting action on CYP 450 and P-glycoprotein efflux pump. Solubility of Tacrolimus was determined in various vehicles, including oils, surfactants and cosolvents. Pseudoternary phase diagrams were constructed to identify the most efficient self-emulsification region. The optimized formulations were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and globule size analysis. The optimized liquid SMEDDS formulation contained 20% Phosal 53 MCT as oil, 60% Tween 20 as surfactant and 20% ethanol as cosolvent. Liquid SMEDDS was converted to solid SMEDDS by using Aerosil-200 and Florite-RE as inert solid adsorbents. The optimized liquid and solid SMEDDS showed higher drug release than the marketed capsule and pure API powder. For optimized liquid SMEDDS and solid SMEDDS, the globule sizes were found to be 140.9 nm and 304.6 nm, respectively. DSC and XRD results of solid SMEDDS confirmed that the drug present in the formulation was in an amorphous state. Shelf-lives for liquid SMEDDS and solid SMEDDS were found to be 1.76 and 2.27 years, respectively. The prepared liquid SMEDDS and solid SMEDDS containing bioenhancer excipients increase the in vitro dissolution rate of lipophilic Tacrolimus.