The Research And Preparation Of Hydroxycamptothecin Emulsion For Intraveneous

10-hydroxycamptothecin(HCPT) is extracted from camptotheca acuminata Decaisne. HCPT has been tested widely effective against cancers such as live cancer, stomach cancer and leucocythemia etc. Now HCPT injection is used as first-line optimal anti-cancer drugs in clinic. However, due to its poor solubility in water and oil, HCPT on shelve is its carboxylate form in NaOH solution. Many serious clinical problems have been caused such as lower anti-cancer activity, frequent administration and gastrointestinal side effect to decrease its clinical application. In order to reduce side effect and its carboxylate form in solution, HCPT emulsion for intraveneous is prepared in present study, including:1 Preformulation research of HCPT emulsion for intraveneous.A precise and convenient HPLC method in-vitro, dissociation equilibrium constant in different pH PBS, solubility in different oils, apparent distribution coefficient in N-octanol/water and N-octanol/saline solution have been studied to provide the basis for prescription design, process conditions determination and in-vivo analysis establishment.2 Formulation design and preparation techniques of HCPT emulsion for injectionSingle factor analysis was employed to evaluated the influence of different kinds of phospholipid and oils. In the preparation techniques research, the influence of emulsification methods, temperature, homogenization press and times was investigated to determine the optimal technique parameters. On the basis of single factor analysis, the formulation was optimized by orthogonal design and the encapsulation parameter was taken as the response. The optimized emulsion was of uniform particle size and high encapsulation.3 In-vitro release and preliminary safety evaluation of HCPT emulsion for injectionCarboxylate form percent of HCPT and in-vitro release of HCPT emulsion in PBS was investigated. In preliminary evaluation, the results of Erythrocyte hemolysis test and abnormal toxicity test showed that HCPT emulsion met the basic safety requirements.4 The pharmacokinetics study of HCPT and Brucea Javanica oil emulsionAfter a single dose of HCPT injection, HCPT emulsion and the mixture of HCPT injection and Brucea Javanica oil emulsion, the pharmacokinetics study results showed that HCPT injection disappeared from circulation within 2h due to its short half-life (30 min). In contrast, HCPT emulsion showed a longer circumulation time and significantly increased bioavailability of HCPT, which will contribute to the increased therapeutic effect of CPTs.5 Biodistribution of HCPT emulsionAfter a single dose of HCPT injection, HCPT emulsion and the mixture of HCPT injection and Brucea Javanica oil emulsion, the biodistribution results showed that the distribution of HCPT in mice was significantly changed. After intraveneous injection, HCPT emulsion was readily to uptake by reticuloendothelial system (RES) and accumulated in liver and spleen, which will increase local drug concentration and reduce systemic toxicity clinically.