Development of sarpogrelate external preparation for intractable pain control. I. Pre-formulation study on application of modified beta-cyclodextrins.
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 beta-CD resulted in suppressed SPG hydrolysis. Addition of sulfobutylether-beta-CD (SBE-beta-CD, Captisol had the most significant stabilization effect. Phase solubility diagram and (1)H-NMR analyses indicated that dimethyl-beta-CD and SBE-beta-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-beta-CD was determined to be the most suitable solubilizing agent for external SPG preparation.
Hanawa
Kazumi
K
Department of Pharmacy, University Hospital, University of Yamanashi, Yamanashi, Japan.
Hanawa
Takehisa
T
Tsuchiya
Chikako
C
Higashi
Kenjirou
K
Suzuki
Masahiko
M
Moribe
Kunikazu
K
Yamamoto
Keiji
K
Oguchi
Toshio
T
D000700:Analgesics / Q000737:chemistry*; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D006868:Hydrolysis; D010148:Intractable Pain / Q000188:drug therapy; D044367:Phase Transition; D012702:Serotonin Antagonists / Q000737:chemistry*; D012995:Solubility; D013386:Succinates / Q000737:chemistry*; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000700:Analgesics; D005079:Excipients; D012702:Serotonin Antagonists; D013386:Succinates; D047392:beta-Cyclodextrins; C064294:sarpogrelate