Preparation Of Praziquatel-Hydroxypropyl-β-Cyclodextrin Inclusion Complex

Praziquatel (PZQ) is most effective anti-schistosome drug so far, while it's poor solubility and bioavailibility discount it's clinical effect. Hydroxypropyl-β-cyclodextrin (HP-β-CD), as a kind of promising soluable medical supplement material, is often used to include some guest molecule to improve guest's solubility and soluable velocity. This thesis aimed at prepareing PZQ-HP-β-CD inclusion complex, identifying this inclusion complex and establishing quality standards system. The main tests and results were as follows.During the preparation of PZQ-HP-β-CD inclusion complex, through compare and contrast of three viable methods,Ultrasonication was chosen firstly, then the factors which influenced preparation were studied one by one and the main three factors were find out. Finally, the orthogonal design and analysis of variance on the main factors was done to optimize the preparation procedure, the optimum procedure were: the ratio of host/guest molecules was 2.0:1, solvent was 80% ethanol, inclusion time was 30 min. The inclusion complex made in this way was stable and it's solubility was enhanced significantly.With the purpose of further investigating the inner constructure and inclusion mechanism, inclusion complexes were identified by phase solubility analysis, melting point detect, infrared spectrophotometry and thin chromatogram, the results infered that PZQ was set into HP-β-CD molecular cavity as guest, and this inlusion complex was different from simple physical fixture of PZQ and HP-β-CD. In this inlusion complex supermolecular system, the host and guest bonded at 1:1 molecules ratio, the inclusion index was 145.Content of PZQ in inlusion complex was determined with ultra-vioiet spectro- photometry.Equation of calibration curve was: A=0.0215+1.2128 C( r=0.9999,n = 5).The average method recovery was 95.8%, the precision of within-day and the precision of day-to-day were 1.99% and 2.90% respectively. This method was proved to be satable and precise way to determine the PZQ content which was 9.84% valued by this method. The average dissolution percentage and velocity of PZQ-HP-β-CD inclusion complex were higher than that of common PZQ tablet. Accelerated stability experiment indicated that PZQ-HP-β-CD inclusion complex was considerable stable to light, heat and humid condition. Classical constant temperature heating stability experiment told that period of validity of PZQ-HP-β-CD inclusion complex was 5.3 years. What's more, the clinical security of inclusion complex was estimated on chicken, the most endurable dosage of PZQ was 6.0g/Kg which was as 300 time as the clinical recommended dosage. As a result, PZQ-HP-β-CD inclusion complex was regarded as actually innoxious.