Micronization of cilostazol using supercritical antisolvent (SAS) process: Effect of process parameters

• Published in: Powder technology 2007-08, Vol.177 (2), p.64-70
• Main Authors: Kim, Min-Soo, Lee, Sibeum, Park, Jeong-Sook, Woo, Jong-Soo, Hwang, Sung-Joo
• Format: Article
• Language: English
• Subjects: Applied sciences; Chemical engineering; Cilostazol; Exact sciences and technology; Micronization; Miscellaneous; Poorly water-soluble drug; Solid-solid systems; Supercritical antisolvent
• ISSN: 0032-5910; 1873-328X
• DOI: 10.1016/j.powtec.2007.02.029

The aim of this study was to improve dissolution rate of poorly water-soluble drug, cilostazol, using supercritical antisolvent (SAS) process. The effect of process variables, such as pressure, temperature, drug concentration, type of solvents, feed rate ratio of CO 2/drug solution, on drug particle formation during SAS process was investigated. Particles with mean particle size ranging between 0.90 and 4.52 μm were obtained by varying process parameters such as precipitation vessel pressure and temperature, drug solution concentration, solvent type, feed rate ratio of CO 2/drug solution. In particular, mean particle size and distribution were markedly influenced by drug solution concentration during SAS process. Moreover, the drug did not change its crystal form and the operating parameters might control the ‘crystal texture’ due to the change in crystallinity and preferred orientation during SAS process, as confirmed by differential scanning calorimetry and powder X-ray diffraction study. In addition, the dissolution rate of drug precipitated using SAS process was highly increased in comparison with unprocessed drug. Therefore, it is concluded that the dissolution rate of drug is significantly increased by micronization of cilostazol, leading to the reduction in particle size and increased specific surface area after SAS process. Micronization with supercritical antisolvent process resulted in a significant decrease in mean particle size, as compared to unprocessed drug. The dissolution rates of drug precipitated from both dichloromethane and glacial acetic acid are highly increased in comparison with unprocessed drug due to reduction in particle size and a higher surface to dissolution medium. [Display omitted]