TITLE:
Formulation Development and In-Vivo Evaluation of Atorvastatin Calcium Solid Dispersion in Streptozotocin Induced Diabetic Mice
AUTHORS:
Md. Shahin Sarker, Ranjan Kumar Barman, Md. Ashraf Ali, Shuji Noguchi, Yasunori Iwao, Shigeru Itai, Mir Imam Ibne Wahed
KEYWORDS:
Solid Dispersion, Atorvastatin, Poor Aqueous Solubiity, Streptozotocin, Diabetic Mice
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.9 No.9,
September
30,
2018
ABSTRACT:
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.