Optimization of compounded nanosuspension of paclitaxel and betulinic acid by Box-Behnken design-response surface method / 中草药

ABSTRACT

Objective: To prepare compounded nanosuspensions of paclitaxel and betulinic acid nanosuspension and optimize the preparation process. Methods: Nanosuspension was prepared by high pressure homogenization with poloxamer 188 and lecithin as stabilizer. Stabilizer concentration, stabilizer ratio, homogeneous pressure, and cycle times were selected as investigation factors and the particle size and PDI of nanosuspension were selected as evaluation index to optimize the prescription by Box-Behnken design-response surface method and the in vitro evaluation was determined. Results: The optimal formulation was as follows stabilizer concentration 0.6 mg/mL, poloxamer 188-lecithin (2∶1), homogenous pressure 100 MPa, cycle times 20 times. The average particle size was (282.54 ± 5.40) nm, PDI was 0.242 ± 0.020. The nano-particles in the paclitaxel-betulinic acid compounded nanosuspension were rod-shaped. The nanosuspension had perfect redispersibility and satisfactory short-term stability. Paclitaxel and betulinic acid in nano lyophilized powders all existed in amorphous form. After being prepared into nanosuspension formulation, the solubility of paclitaxel in water was increased by about 90 times while that of betulinic acid was increased by about 100 times. In 2 h, the cumulative dissolution rate of paclitaxel and betulinic acid in nanosuspension of paclitaxel and betulinic acid were all up to 95%. Conclusion: Optimizing the preparation process of nano-suspension with Box-Behnken design-response surface method is effective and feasible and nanosuspension formulation can improve the dissolution of paclitaxel and betulinic acid observably.