Coamorphous Atorvastatin Calcium to Improve its Physicochemical and Pharmacokinetic Properties

Ali Shayanfar1, Hamed Ghavimi2, Hamed Hamishekar3, Abolghasem Jouyban4

1Faculty of Pharmacy, Students' Research Committee, 3Liver and Gastrointestinal Diseases Research Center and 4Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2Liver and Gastrointestinal Diseases Research Center and 4Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
3Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
4Faculty of Pharmacy; Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract


Purpose: Atorvastatin calcium (ATC) is classified as class II (low solubility and high permeability) compound according to the biopharmaceutical classification system. The amorphous form of ATC possesses higher solubility, dissolution rate, and bioavailability than its crystalline form. Coamorphous drug system is a new and emerging method to prepare stable amorphous forms, in this case leading to the improved stability of ATC in dissolution medium. Methods: In this study, coamorphous form of ATC and nicotinamide (ATC-NIC) was  prepared from solvent evaporation method and characterized using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and powder X-ray diffraction (PXRD). The intrinsic dissolution rate and solubility of ATC-NIC were determined along with plasma concentrations of ATC using HPLC after oral dosing in rats. Results: The crystalline ATC was converted to coamorphous form revealing a molecular interaction between ATC and NIC. The intrinsic dissolution rate, solubility and plasma concentration of coamorphous ATC-NIC are higher than those of crystalline ATC. ATC-NIC coamorphous system showed greater solution stability than those reported in the literature for amorphous ATC.   Conclusions: Coamorphous ATC-NIC has improved physicochemical and pharmacokinetic properties as compared to ATC.

 

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J Pharm Pharm Sci, 16 (4): 577-587, 2013

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