Preparation of amorphous indomethacin from aqueous 2,6-di-O-methyl-beta-cyclodextrin solution

Int J Pharm. 2008 Apr 16;354(1-2):70-6. doi: 10.1016/j.ijpharm.2007.11.010. Epub 2007 Nov 17.

Abstract

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".

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemistry*
  • Chemical Precipitation
  • Chemistry, Pharmaceutical
  • Crystallization
  • Cyclodextrins / chemistry
  • Drug Stability
  • Drug Storage
  • Indomethacin / chemistry*
  • Pharmaceutical Solutions
  • Solubility
  • Time Factors
  • Water / chemistry
  • beta-Cyclodextrins / chemistry*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclodextrins
  • Pharmaceutical Solutions
  • beta-Cyclodextrins
  • Water
  • heptakis(2,6-O-dimethyl)beta-cyclodextrin
  • Indomethacin