Preparation And Evaluation Of Lovastatin Inclusions And Their Tablets

Hyper cholesterolemia is the most dangerous disease that threaten human being and has close relationship with other cardiovascular diseases. How effectively and low-costly cure the hyper cholesterolemia disease is the persistent goal of pharmacists. Lovastatin is the object of this study. We investigated its basic pharmaceutical properties; prepared lovastatin-β-cyclodextrin inclusion and its inclusion tablets; studied the influence of inclusion tablets on normal animal blood. Results are showed as follows:(1) Determination of lovastatin's solubilities in different resolvents: using UV spectrophotometric method, we determined the solubilities of lovastatin in water, n-propanol-Phosphate buffer, 0.5% Sodium dodecyl sulfate solution. The results showed that lovastatin has high solubility in 0.5% Sodium dodecyl sulfate solution, but insolvable in water, the solubility was 2.14×10-3mg/ml.(2) Lipid water partition coefficient of lovastatin in different pH : Water dissolubility is necessary to drugs to transport into blood or body fluids, other drugs possess lipid dissolubility to pass biological lipid membrane. The relative extent of lipid solubility and water solubility was defined as lipid water partition coefficient. This experiment determines lipid water partition coefficient through flask-HPLC method. The results showed that under near physiological environment, lipid water partition coefficient of lovastatin was 3.72.(3) Study on lovastatin-β-cyclodextrin inclusion: The orthogonal experimental design was adopted in the determination of inclusion procedure, and prepared inclusion under the best parameters. We determined the lovastatin-β-cyclodextrin inclusion by microscopy method, infrared spectroscopy and X-ray diffraction analysis. We used UV spectroscopic method to determine the lovastatin in lovastatin-β-cyclodextrin inclusion and the stability of inclusion. The results are as follows: lovastatin-β-cyclodextrins was a new substance different from lovastatin and cyclodextrin. The encapsulation of Lovastatin was about 87% and the load of lovastatin in the inclusion complex was about 20%, which approximated to the theoretical values. The stability of lovastatin-β-cyclodextrins and lovastatin were both meet the requirements of new drugs in pharmacopeia.(4) Preparation of inclusion tablets: Estimated by dissolution rates, using...