Preparation and pharmacokinetics evaluation of oral self-emulsifying system for poorly water-soluble drug Lornoxicam.

Fei Li, Shuangshuang Song, Yingxin Guo, Qianqian Zhao, Xuemei Zhang, Weisan Pan, Xinggang Yang

Drug delivery 2015

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The present work was performed aiming to develop a new solid self-emulsifying system (SMEDDS) for poorly water-soluble drug Lornoxicam and evaluate the bioavailability in Wister rats by oral gavage. Liquid SMEDDS of Lornoxicam was formulated with Labrafil M 1944 CS as oil phase, Kolliphor HS 15 as a surfactant and Transcutol HP as a cosurfactant after screening various vehicles. The microemulsion system selected from the phase diagram and optimized by central composite design (CCD) response surface method was transformed into solid-SMEDDS (S-SMEDDS) by lyophilization using sucrose as cryoprotectant. The formulations were further characterized by the particle size, poly dispersity index (PDI), self-emulsifying time, zeta potential, transmission electron microscope (TEM), differential scanning calorimeter (DSC), in vitro drug release and in vivo pharmacokinetics. Results of DSC studies confirmed that the drug was incorporated in the S-SMEDDS. The in vitro drug release from Lornoxicam SMEDDS was found to be greatly higher in comparison with that from the commercial tablets. It was indicated that SMEDDS might be effective in reducing the effect of pH variability of Lornoxicam and improving the release performance of Lornoxicam. HPLC system was applied to study the concentration of Lornoxicam in the plasma of the Wister rats after oral administration of Lornoxicam SMEDDS and Lornoxicam commercial tablets. The pharmacokinetics parameters of the rats were C(max) 1065.91 ± 224.90 and 1855.22 ± 748.25 ngmL(-1), T(max) were 2.5 ± 0.4 h and 1.8 ± 0.5 h, and AUC(0∼t) were 5316.35 ± 323.62 and 7758.07 ± 241.57 ngmL(-1) h, respectively. Calculated by AUC(0∼∞), the relative bioavailability of Lornoxicam S-SMEDDS was 151.69 ± 15.32%. It suggested that this S-SMEDDS could be used as a successful oral solid dosage form to improve the solubility and bioavailability of poorly water-soluble drug Lornoxicam as well.

Citation

Fei Li, Shuangshuang Song, Yingxin Guo, Qianqian Zhao, Xuemei Zhang, Weisan Pan, Xinggang Yang. Preparation and pharmacokinetics evaluation of oral self-emulsifying system for poorly water-soluble drug Lornoxicam. Drug delivery. 2015;22(4):487-98