Phase behavior of water-insoluble simvastatin drug in supercritical mixtures of chlorodifluoromethane and carbon dioxide

Dong-Joon Oh; Byung-Chul Lee; Sung-Joo Hwang

Korean Journal of Chemical Engineering, Vol.23, No.6, 1009-1015, November, 2006

DOI10.1007/s11814-006-0022-2 Export Citation

Phase behavior of water-insoluble simvastatin drug in supercritical mixtures of chlorodifluoromethane and carbon dioxide

Dong-Joon Oh, Byung-Chul Lee^†, and Sung-Joo Hwang¹

Department of Chemical Engineering and Nano-Bio Technology, Hannam University, 133 Ojung-dong, Daeduk-gu, Daejeon 306-791, Korea
¹College of Pharmacy, Chungnam National University, 220 Kung-dong, Yusong-gu, Daejeon 305-764, Korea

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Phase behavior data are presented for simvastatin, a water-insoluble drug, in supercritical solvent mixtures of chlorodifluoromethane (CHClF2) and carbon dioxide (CO2). The solubilities of the simvastatin drug in the solvent mixtures of CHClF2 and CO2 were determined by measuring the cloud point pressures using a variable-volume view cell apparatus as functions of temperature, solvent composition, and amount of the drug loaded into the solution. The cloud point pressure increased with increasing the system temperature. As the CHClF2 composition in the solvent mixture increased, the cloud point pressure at a fixed temperature decreased. Addition of CHClF2 to CO2 caused an increase of the dissolving power of the mixed solvent for the simvastatin drug due to the increase of the solvent polarity. CHClF2 acted as a solvent for simvastatin, while CO2 acted as an anti-solvent. The cloud point pressure increased as the amount of the simvastatin drug in the solvent mixture increased. Consequently, the solubility of the simvastatin drug in the solvent mixture of CHClF2 and CO2 decreased with increasing the CO2 content in the solvent mixture as well as with increasing the system temperature.

Keywords:Simvastatin;Water-insoluble Drug;Solubility;Supercritical Fluid;Carbon Dioxide;Chlorodifluoromethane;Cloud Point Pressure

[References]

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Datea AA, Patravale VB, Curr. Opin. Colloid Interface Sci., 9, 222 (2004)
Duarte ARC, Costa MS, Simplicio AL, Cardoso MM, Duarte CMM, Int. J. Pharm., 308, 168 (2006)
Fages J, Lochard H, Letourneau JJ, Sauceau M, Rodier E, Powder Technol., 141(3), 219 (2004)
Ginty PJ, Whitaker MJ, Shakesheff KM, Howdle SM, Materials Today, 8, 42 (2005)
Guney O, Akgerman A, AIChE J., 48(4), 856 (2002)
Huang Z, Sun GB, Chiew YC, Kawi S, Powder Technol., 160(2), 127 (2005)
Kerc J, Srcic S, Knez Z, Sencar-Bozic P, Int. J. Pharm., 182, 33 (1999)
Kwak H, Jung JW, Bae SY, Kumazawa H, Korean J. Chem. Eng., 21(6), 1245 (2004)
Lee BC, Kim NI, Korean J. Chem. Eng., 19(1), 132 (2002)
Lee JM, Lee BC, Hwang SJ, J. Chem. Eng. Data, 45, 1162 (2000)
Lee JM, Lim JS, Lee YW, J. Chem. Eng. Data, 48, 774 (2003)
Miguel F, Martin A, Gamse T, Cocero MJ, J. Supercrit. Fluids, 36, 225 (2006)
Perrut M, Jung J, Leboeuf F, Int. J. Pharm., 288, 3 (2005)
Reverchon E, Adami R, J. Supercrit. Fluids, 37, 1 (2006)
Reverchon E, Della Porta G, J. Supercrit. Fluids, 26, 243 (2003)
Reverchon E, Spada A, Powder Technol., 141(1-2), 100 (2004)
Rodier E, Lochard H, Sauceau M, Letourneau JJ, Freiss B, Fages J, Eur. J. Pharm. Sci., 26, 184 (2005)
Shekunov BY, York P, J. Cryst. Growth, 211, 122 (2000)
Song KH, Lee CH, Lim JS, Lee YW, Korean J. Chem. Eng., 19(1), 139 (2002)
Steckel H, Pichert L, Muller BW, Eur. J. Pharm. Biopharm., 57, 507 (2004)
Thakur R, Gupta RB, Int. J. Pharm., 308, 190 (2006)
Turk M, Hils P, Helfgen B, Schaber K, Martin HJ, Wahl MA, J. Supercrit. Fluids, 22, 75 (2002)
Van Nijlen T, Brennan K, Van den Mooter G, Blaton N, Kinget R, Augustijns P, Int. J. Pharm., 254, 173 (2003)
Won DH, Kim MS, Lee S, Park JS, Hwang SJ, Int. J. Pharm., 301, 199 (2005)
Yeo SD, Kiran E, J. Supercrit. Fluids, 34, 287 (2005)

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