Preparation of amorphous indomethacin from aqueous 2,6-di-O-methyl-beta-cyclodextrin solution.
Indomethacin precipitated exclusively in an amorphous form from aqueous 2,6-di-O-methyl-beta-cyclodextrin solutions, whereas it precipitated in Form V polymorph from the solutions of the drug alone, parent cyclodextrins and 2-hydroxypropyl-cyclodextrins. The polymorphic transition of the amorphous form to Form V crystals in aqueous solution was markedly inhibited by the addition of 2,6-di-O-methyl-beta-cyclodextrin, keeping the amorphous state for at least 5 days at 4 degrees C, whereas it quickly transformed to Form V crystals in the absence of 2,6-di-O-methyl-beta-cyclodextrin. 2,6-Di-O-methyl-beta-cyclodextrin suppressed the solution-mediated polymorphic transition of amorphous form of indomethacin to Form V crystals in aqueous solution. The current results suggested that 2,6-di-O-methyl-beta-cyclodextrin is useful for isolation of amorphous indomethacin that occurs at an early stage of crystallization according to "Ostwald's Rule of Stages".
Iohara
Daisuke
D
Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, Japan.
Hirayama
Fumitoshi
F
Ishiguro
Takako
T
Arima
Hidetoshi
H
Uekama
Kaneto
K
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D003505:Cyclodextrins / Q000737:chemistry; D004355:Drug Stability; D004356:Drug Storage; D007213:Indomethacin / Q000737:chemistry*; D019999:Pharmaceutical Solutions; D012995:Solubility; D013997:Time Factors; D014867:Water / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003505:Cyclodextrins; D019999:Pharmaceutical Solutions; D047392:beta-Cyclodextrins; D014867:Water; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin; D007213:Indomethacin