Solubility of some statin drugs in supercritical carbon dioxide and representing the solute solubility data with several density-based correlations

Solubility of some statin drugs in supercritical carbon dioxide and representing the solute solubility data with several density-based correlations
Received 5 August 2006; revised 23 September 2006; accepted 16 October 2006. Available online 17 November 2006.
Mohammad Hojjatia, Yadollah Yaminia, , , Mostafa Khajeha and Alireza Vatanarab
The Journal of Supercritical Fluids
Article in Press
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Copyright ? 2006 Elsevier B.V. All rights reserved.
aDepartment of Chemistry, School of Sciences, Tarbiat Modarres University, P.O. Box 14115-175, Tehran, Iran
bDepartment of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Accurate experimental determination of a solid drug's solubility in supercritical fluids (SCFs) and its correlation is crucially important to the development of supercritical technologies for the pharmaceutical industry. In this work, the solubilities of lovastatin, simvastatin, atorvastatin, rosuvastatin and flovastatin in supercritical carbon dioxide (SC-CO2) were obtained using a simple static method. The solubility measurements were performed at pressures in the range of 121.6?354.6 bar and temperatures in the range of 308?348 K. The mole fraction solubilities ranged from 1.12 ? 10-6 to 1.45 ? 10-3. Solubility data were correlated using four semi-empirical density-based models (Chrastil model, Bartle model, K?J model and M?T model). The results showed that by using three temperature-independent parameters these models can be applied for satisfactory solubility predictions at different pressures and temperatures. A comparison among the four models revealed that the Bartle and M?T models gave much better correlations of the solubility data with an overall average absolute relative deviation (AARD%) of 6.3 and 8.8%, respectively. Using the correlation results, the heat of drug?CO2 solvation and that of drug vaporization were separately approximated in the range of 13.2?21.3 and 50.5?101.3 kJ/mol.
Keywords: Lovastatin; Simvastatin; Atorvastatin; Rosuvastatin; Flovastatin; Solubility; Supercritical carbon dioxide

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