Solid -state acid -base reactions of indomethacin and flufenamic acid
Abstract
The purpose of this study is to understand the mechanism of solid-state acid-base reactions and identify controlling factors for this type of reaction. The reactions between indomethacin and sodium bicarbonate, indomethacin and sodium carbonate, and flufenamic acid and magnesium oxide were investigated using X-ray powder diffraction, Fourier transform infrared spectroscopy, thermogravimetry, and solid-state nuclear magnetic resonance spectrometry. Quantitative methods based on those techniques were established to characterize those solid-solid reactions. Surface migration followed by diffusion is proposed to be the possible mechanism, which is strongly supported by dependence of reactivity on particle size and mixing ratio. Relative humidity was identified to be very critical for acid-base reactions. This type of reaction will be very slow if both reactants can be kept dry. Different polymorphs and habits may have different reactivity. Solid-gas acid-base reactions with ammonia provided more clear understanding for the role of polymorphs. Accessibility of reaction groups may be very important for the stability. It was proposed that the acid-base reactions are initiated at defect sites. Residual amounts of amorphous content may be very critical, so a quantitative method for residual amorphous form was developed using parallel beam X-ray powder diffraction and whole pattern fitting. With lactose as a model system, the detection limit can reach 0.37% by the method developed.
Degree
Ph.D.
Advisors
Byrn, Purdue University.
Subject Area
Analytical chemistry|Physical chemistry|Organic chemistry
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