2010 Volume 58 Issue 1 Pages 45-50
To optimize the formulation of in-hospital sarpogrelate (SPG) preparation for external use, various cyclodextrins (CDs) were investigated for their ability to improve the aqueous solubility and chemical stability of SPG. Although hydrolysis of SPG was markedly accelerated at above pH 7.0 in aqueous solution, the addition of modified β-CD resulted in suppressed SPG hydrolysis. Addition of sulfobutylether-β-CD (SBE-β-CD, Captisol®) had the most significant stabilization effect. Phase solubility diagram and 1H-NMR analyses indicated that dimethyl-β-CD and SBE-β-CD formed significantly stable inclusion complexes with SPG in aqueous solution, thereby contributing to both the increased solubility and chemical stabilization of SPG. In terms of the clinical safety of CD derivatives, SBE-β-CD was determined to be the most suitable solubilizing agent for external SPG preparation.
