Preparation Of Atorvastatin Salt And In Vitro Evaluation

Objective:Atorvastatin is a HMG-CoA reductase-selective inhibitor,which can significantly reduce the level of cholesterol and lipoprotein lipids,reduce the generation of low density lipoprotein cholesterol(hdl-c).Clinically,it is used for familial hypercholesterolemia,combined hyperlipidemia.But due to the poor water solubility,its bioavailability is rather low.In this study,atorvastatin is prepared by salification technology,the water solubility and in vitro release are impoved.Methods:The active ingredients of atorvastatin are organic acids,its proton transfers from acidic component to basic component and complex is formed through the ionic bond between atorvastatin and base.Solvent-antisolvent method is used in this paper to investigate atorvastatin salt,eight alkalis are screened such as sodium bicarbonate,lysine and arginine etc.The eight alkalis are mixed with the drugs in soluble solutions to varying proportion,and then precipitated in crystalline form by introducing various different desolvations.Optimal extracting time point was determined by thin layer chromatography(TLC),atorvastatin salt are obtained by vacuum suction filter technology.Atorvastatin sodium,atorvastatin arginin,atorvastatin lysine is screened,then determine the cumulative release in vitro and carry on the stability test.Results:Atorvastatin sodium,atorvastatin arginin,atorvastatin lysine were screened by salification technology,and their best preparation were determined.The water solubility of atorvastatin sodium was 477.64±44.08 g/mL,cumulative in vitro release was 60.96±3.00%;the water solubility of atorvastatin arginin was 704.58±21.56 g/mL,the cumulative release in vitro was 94.76±1.81%;the water solubility of atorvastatin lysine was 507.97±41.33 g/mL,the cumulative release in vitro was 98.39±0.46%.Stability test showed that the stability of atorvastatin sodium was excllent.Drug content and superficial phenomenon of atorvastatin arginin,atorvastatin lysine under the condition of high temperature,strong light were no obvious change;Moisture adsorption was obvious under the condition of high humidity.Conclusion:The water solubility and the release degree in vitro of the atorvastatin sodium,atorvastatin arginin,atorvastatin lysine prepared by drug salification technology are significantly higher than that of active pharmaceutical ingredient and marked atorvastatin calcium.This preparation method turns out to be manipulated conveniently,providing certain theoretical basis and experimental technical supports for the solution of refractory of atorvastatin and the development of preparations.