Solid self-nanoemulsifying cyclosporin A pellets prepared by fluid-bed coating: preparation, characterization and in vitro redispersibility

Yang Lei^1,2, Yi Lu², Jianping Qi², Sufang Nie¹, Fuqiang Hu³, Weisan Pan¹, Wei Wu^2
1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang; ²School of Pharmacy, Fudan University, Shanghai; ³School of Pharmacy, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China

Background: The objective of this study was to evaluate fluid-bed coating as a new technique to prepare a pellet-based solid self-nanoemulsifying drug delivery system (SNEDDS) using cyclosporin A as a model of a poorly water-soluble drug.
Methods: The rationale of this technique was to entrap a Liquid SNEDDS in the matrix of the coating material, polyvinylpyrrolidone K30, by fluid-bed coating. Pseudoternary phase diagrams were used to screen the liquid SNEDDS formulations. The optimal formulation was composed of Labrafil M^® 1944 CS, Transcutol P^®, and Cremophor^® EL in a ratio of 9:14:7. To prepare solid SNEDDS pellets, liquid SNEDDS was first dispersed in an aqueous solution of polyvinylpyrrolidone and then sprayed onto the surface of non-pareil pellets. Upon evaporation of water, polyvinylpyrrolidone precipitated and formed tight films to entrap the liquid SNEDDS. Visual observation and scanning electron microscopic analysis confirmed good appearance of the solid SNEDDS pellets.
Results: Our results indicated that up to 40% of the liquid SNEDDS could be entrapped in the coating layer. Powder x-ray diffraction analysis confirmed nonexistence of crystalline cyclosporin A in the formulation. Solid SNEDDS pellets showed a slower redispersion rate than the liquid SNEDDS. An increase in the total liquid SNEDDS loading led to faster redispersion, whereas increased coating weight (up to 400%) significantly decreased the redispersion rate. Both cyclosporin A loading and protective coating with 5% polyvinylpyrrolidone K30 did not significantly affect the redispersion rate.
Conclusion: It is concluded that fluid-bed coating is a new technique with considerable potential for preparation of pellet-based solid SNEDDS formulations.

Keywords: solid, self-nanoemulsifying, fluid-bed coating, cyclosporin A, pellets