Dilpreet Singh, Kusha Sharma and Neena Bedi Pages 24 - 38 ( 15 )
Objective: The aim of this study was to develop and evaluate self microemulsifying drug delivery system (SMEDDS) to improve oral bioavailability of tacrolimus.Methods: The solubility of tacrolimus in various oils, surfactants and co-surfactants was determined and self-microemulsion preconcentrates were prepared. Pseudo-ternary phase diagrams were constructed to identify stable microemulsion region. The prepared formulations were evaluated for optical clarity, zeta potential, droplet size, viscosity and stability and converted into solid form by the spray drying method and characterized for various parameters. In vitro drug release and pharmacokinetic studies were also carried out to determine the dissolution rate and oral bioavailability. Results: The optimized formulation contained 13.15% w/w of oil phase, 52.21% w/w of Smix and 36.84 % w/w of co-surfactant producing a stable and transparent microemulsion with a percent transmittance, droplet size and zeta potential 99.23%, 52.15 nm and -10.19 mV, respectively. The solid SMEDDS showed colloidal and spherical nature in scanning electron microscopy. X-ray diffraction and differential scanning calorimetry exhibited an amorphous form of drug in solid SMEDDS. In vitro dissolution studies indicated multi folds increase in dissolution rate in liquid and solid SMEDDS as compared to marketed product and API (P < 0.05). Both liquid and solid SMEDDS were stable after three months of storage at different temperature conditions. In vivo pharmacokinetic studies revealed three fold enhanced AUC0-24h, Cmax and Tmax as compared to marketed product (P < 0.05). Conclusion: The results suggested that the prepared SMEDDS formulations could be used as a promising vehicle for improving the solubility and oral bioavailability of tacrolimus.
Tacrolimus, preconcentrates, spray drying, solid SMEDDS, bioavailability.
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar (143005), Punjab