Atorvastatin calcium (ATV) is a selective competitive inhibitor of HMG CoA reductase characterized by poor aqueous solubility leading to inadequate bioavailability. The present study was designed to develop solid disp...Atorvastatin calcium (ATV) is a selective competitive inhibitor of HMG CoA reductase characterized by poor aqueous solubility leading to inadequate bioavailability. The present study was designed to develop solid dispersion of atorvastatin (SDA) to improve the solubility and dissolution properties of ATV and evaluation of its in-vivo efficiency in streptozotocin (STZ) induced diabetic mice. Formulations of SDA were prepared by solvent evaporation method using PEG-4000 alone and/or mixture of PEG-4000 and Carplex-80 as carrier in different ratios. Solid-state analyses of SDA were performed to characterize the physicochemical properties of newly developed SDA by differential scanning calorimetry (DSC), powder x-ray diffractometry (PXRD), fourier transformed infrared spectra (FTIR) and scanning electron microscopy (SEM). DSC and PXRD showed that the crystallinity of drugs was notably decreased during the preparation of SDA. FTIR and SEM also demonstrated the conversion of ATV from amorphous to crystalline state resulting in improved solubility. Among formulations, SDA-5 showed significant enhancement of in-vitro drug release (around 2 fold higher) as compared to pure ATV. Further, in-vivo study was conducted to evaluate the effects of a newly developed ATV loaded solid dispersion on glycemic control, lipid profile, liver enzyme and histopathology in STZ induced diabetic mice. Oral administration of SDA significantly lowered the blood glucose levels during the course of treatment. Treatment with SDA significantly improved lipid profiles better than ATV alone and the effect was dose-dependent. After one week of SDA treatment significantly decreased liver weights as result of lipid clearance and the hepatocytes regained their normal architecture, and these beneficial effects can be correlated with the reduction of SGPT levels. The results demonstrated that, SDA exerted better glycemic control, lipid lowering effect and organ protection (liver and pancreas) than that of conventional ATV in STZ induced diabetic mice. The mechanism by which SDA conferred better improvement in diabetic conditions can be partially explained by enhancement of solubility and dissolution rate when ATV is loaded in solid dispersion.展开更多
文摘Atorvastatin calcium (ATV) is a selective competitive inhibitor of HMG CoA reductase characterized by poor aqueous solubility leading to inadequate bioavailability. The present study was designed to develop solid dispersion of atorvastatin (SDA) to improve the solubility and dissolution properties of ATV and evaluation of its in-vivo efficiency in streptozotocin (STZ) induced diabetic mice. Formulations of SDA were prepared by solvent evaporation method using PEG-4000 alone and/or mixture of PEG-4000 and Carplex-80 as carrier in different ratios. Solid-state analyses of SDA were performed to characterize the physicochemical properties of newly developed SDA by differential scanning calorimetry (DSC), powder x-ray diffractometry (PXRD), fourier transformed infrared spectra (FTIR) and scanning electron microscopy (SEM). DSC and PXRD showed that the crystallinity of drugs was notably decreased during the preparation of SDA. FTIR and SEM also demonstrated the conversion of ATV from amorphous to crystalline state resulting in improved solubility. Among formulations, SDA-5 showed significant enhancement of in-vitro drug release (around 2 fold higher) as compared to pure ATV. Further, in-vivo study was conducted to evaluate the effects of a newly developed ATV loaded solid dispersion on glycemic control, lipid profile, liver enzyme and histopathology in STZ induced diabetic mice. Oral administration of SDA significantly lowered the blood glucose levels during the course of treatment. Treatment with SDA significantly improved lipid profiles better than ATV alone and the effect was dose-dependent. After one week of SDA treatment significantly decreased liver weights as result of lipid clearance and the hepatocytes regained their normal architecture, and these beneficial effects can be correlated with the reduction of SGPT levels. The results demonstrated that, SDA exerted better glycemic control, lipid lowering effect and organ protection (liver and pancreas) than that of conventional ATV in STZ induced diabetic mice. The mechanism by which SDA conferred better improvement in diabetic conditions can be partially explained by enhancement of solubility and dissolution rate when ATV is loaded in solid dispersion.
