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Published on: August 15, 2016
Polymorphic transformation of indomethacin under high pressures
Takehiro Okumura1, Masaya Ishida, Kozo Takayama
1Technology Research & Development Center, Dainippon Sumitomo Pharma Co., Kasugade-naka, Konohana-ku, Osaka, Japan. takehiro-okumura@ds-pharma.co.jp
High pressure transforms indomethacin (IMC) forms. Stable alpha-IMC is readily prepared from amorphous IMC slurry under pressure, a novel method for polymorphic screening.
Area of Science:
- Materials Science
- Chemical Engineering
- Crystallography
Background:
- Polymorphism significantly impacts drug properties and efficacy.
- Controlling indomethacin (IMC) polymorphic forms is crucial for pharmaceutical development.
- Stable alpha-IMC is challenging to obtain under ambient conditions.
Purpose of the Study:
- To investigate the effect of high pressure on indomethacin (IMC) polymorphic transformations.
- To explore novel methods for preparing stable indomethacin polymorphic forms.
- To establish a quantitative method for analyzing IMC polymorph mixtures.
Main Methods:
- Compression of intact IMC powders and ethanol slurries (alpha, gamma, amorphous forms) under high pressure.
- Development and application of a quantitative method to determine the percentages of IMC polymorphs.
- Analysis of polymorphic composition in compressed samples.
Main Results:
- Stable alpha-IMC was easily obtained from amorphous IMC ethanol slurry under high pressure.
- Transformation of gamma-IMC to alpha-IMC was observed in ethanol slurry under pressure.
- High pressure favors the more closely-packed alpha-IMC structure and can induce amorphization.
Conclusions:
- High-pressure crystallization from amorphous slurries is an effective strategy for screening solid states.
- Pressure-induced polymorphic transformations offer new avenues for controlling IMC solid forms.
- This approach facilitates the preparation of thermodynamically stable polymorphs.
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