| Objectives Curcumin（CUR）belongs to BCS IV drug,which is insoluble and has low bioavailability.Therefore,curcumin nanocrystals（CUR-NCs）injection is developed by using nanocrystals（NCs）technology,so as to improve the dissolution rate of CUR and bioavailability in vivo.Methods CUR-NCs were prepared by wet grinding with particle size and PDI as evaluation indexes.The formulation and preparation process of CUR-NCs were optimized by Box-Behnken experimental design.Physical and chemical properties of CUR and CUR-NCs were analyzed by scanning electron microscopy,transmission electron microscopy,differential scanning calorimetry,powder X-ray diffraction and Fourier transform infrared spectroscopy.The dissolution behaviors of CUR and CUR-NCs were investigated by paddle method.The in vivo pharmacokinetics of CUR were studied by HPLC-MS/MS.Safety was preliminarily evaluated by CUR-NCs hemolytic and muscle irritation tests.Results 1 CUR was a crystalline compound with multiple diffraction peaks.Its inherent solubility was 0.01（mg/cm2）/min and the cumulative dissolution rate of 10 minutes was8.41%.It is p H dependent and unstable under alkaline conditions.2 Stable CUR-NCs with particle size of 208.3±2.05 nm and PDI of 0.25±0.02 were obtained.3 CUR-NCs showed irregular shape,the crystal form did not change before and after preparation,and the dissolution rate was significantly improved.4 The established analytical methods for the determination of particle size,content and related substances of CUR had been verified to meet the requirements.5 The Cmaxand AUC0-∞of CUR-NCs injection were 4.9 and 4.1times of CUR suspension,respectively.Linear kinetic properties were observed in the dose range of 25～100 mg/kg by descriptive method.6 CUR-NCs with different particle sizes had irregular shapes and consistent crystal forms.The smaller the particle size,the faster the dissolution of CUR-NCs and the higher the bioavailability.7 The hemolysis rate of CUR-NCs injection meets the requirements,with little muscle irritation and good safety.Conclusions In this study,CUR-NCs with particle size of about 200 nm was prepared by wet media grinding method.The formulation process and crystal shape were stable,and the dissolution rate and bioavailability of the drug were significantly improved.CUR-NCs with small particle size was determined to have higher bioavailability and linear kinetic properties in the dose range of 25～100 mg/kg.CUR-NCs injection had good safety.The research work provides ideas for the study of CUR preparation and lays a foundation for the clinical application of CUR.Figure 31;Table 34;Reference 83... |
