Nanocrystals Of Hydroxycamptothecin And Camptothecin Prepared By Supercritical Antisolvent Process

Camptothecin (CPT) and hydroxycamptothecin (HCPT), which isolated from camptothecaacuminata, are both very promising anticancer drugs in the clinical. However, because of theirpoor solubility in water, current clinical applications of CPT and HCPT are formulated as asodium salt of the carboxylate, which exhibited minimal anticancer activity and several sideeffects. Therefore, much effort has been devoted to developing new formulations of CPT andHCPT, and Nanoparticles are effective methods to improve therapeutic efficacy of drugsinsoluble. The supercritical antisolvent (SAS) technique is a new micronized technology. Inthis thesis, HCPT and CPT are selected as model drugs to study the effects of processparameters on preparation of nanocrystals by SAS process.Mixtures of Dichloromethane and Ethanol are selected as solvents, Nanocrystals of HCPTand CPT are successfully prepared by SAS using orthogonal array design or single-factorexperiments, respectively. Sample particles are characterized using laser diffraction particlesize analysis, FT-IR, HS-GC, SEM, XRD, DSC and TGA. The effects of process parameters,including the volume ratio of the mixed solvent (VR), the concentration of the solution (C),the flow rate of solution (F), the precipitation pressure (P) and temperature (T) on the particlesize, morphology and crystalline form are investigated.The results of the orthogonal array design show that the order for the effect of parameterson the particle size of micronized HCPT is as follows: F> VR>T> C> P. The single-factorexperiments indicate that the particle size of micrionized CPT increases with the increase of Fand C, and decreases with the increase of VR and P. The particle size of micronized CPT firstdecreases and then increases with the increase of T. FT-IR results indicate that no significantchange in the chemical structure of processed particles is found, and HS-GC results indicatethat the residual solvent of processed particles is lower than ICH limits. SEM results showthat crystal habit of nanocrystals can be modified by SAS process. The results of XRD, DSCand TGA indicate that polymorphs or the preferred orientation of model drugs can be greatlyaffected by SAS process.The results of this thesis have reference value for theoretical research and application ofpreparation of drug nanocrystals using SAS process.