Enhancement of wettability and dissolution properties of cilostazol using the supercritical antisolvent process: effect of various additives.
The aim of this study was to improve wettability and dissolution rate of a poorly water-soluble drug, cilostazol, using the supercritical antisolvent (SAS) process. The solid state of particles precipitated from dichloromethane containing additives, including poloxamer 188, poloxamer 407, TPGS 1000, Gelucire 44/14 and Gelucire 50/13, in supercritical CO(2) medium were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), FT-IR, particle size analysis, contact angle, and dissolution. Interestingly, the morphology of SAS particles processed with TPGS 1000, Gelucire 44/14 and Gelucire 50/13 changed to plate- or leaflet-shaped. Furthermore, the particle sizes of cilostazol processed with Gelucire 44/14 and Gelucire 50/13 were increased compared to cilostazol processed without additives. Poloxamer 188 and poloxamer 407 were superior in increasing the dissolution rate due to decreased particle size, the resulting increased surface area, and improved wettability. Micronization with the supercritical antisolvent process resulted in a significant decrease in mean particle size, and wettability of cilostazol was increased by using small amounts of hydrophilic additives.
Kim
Min-Soo
MS
Center for Nanotechnology-Based New Drug Dosage Form, College of Pharmacy, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejeon 305-764, Republic of Korea.
Kim
Jeong-Soo
JS
Hwang
Sung-Joo
SJ
D002152:Calorimetry, Differential Scanning; D002245:Carbon Dioxide / Q000737:chemistry; D000077407:Cilostazol; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D010316:Particle Size; D033362:Powder Diffraction; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013777:Tetrazoles / Q000737:chemistry*; D017155:Wettability; D014961:X-Ray Diffraction
D005079:Excipients; D013777:Tetrazoles; D002245:Carbon Dioxide; D000077407:Cilostazol