Development of Sarpogrelate External Preparation for Intractable Pain Control. I. Pre-formulation Study on Application of Modified β-Cyclodextrins

Kazumi Hanawa, Takehisa Hanawa, Chikako Tsuchiya, Kenjirou Higashi, Masahiko Suzuki, Kunikazu Moribe, Keiji Yamamoto, Toshio Oguchi
2010 Chemical and pharmaceutical bulletin  
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 b b-CD resulted in suppressed SPG hydrolysis. Addition of sulfobutylether-b b-CD (SBE-b b-CD, Captisol ® ) had the most significant stabilization effect. Phase
more » ... ility diagram and 1 H-NMR analyses indicated that dimethyl-b b-CD and SBE-b b-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-b b-CD was determined to be the most suitable solubilizing agent for external SPG preparation.
doi:10.1248/cpb.58.45 pmid:20045965 fatcat:gf3f2ta2nfharajknccdvdlu2m