Size reducibility of sulfathiazole by heat transition and subsequent ball-milling.

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In order to examine the feasibility of size reduction by heat transition of polymorphic drugs, crystals of the α-form of sulfathiazole were heated above its transition temperature and the physico-chemical and micromeritical properties of the product were studied by IR spectroscopy, X-ray diffractometry, DSC, BET gas adsorption analysis, and electron microscopy. The original α-crystals became opaque after transition and the polymorphic form of the product was identified as the β-form of sulfathiazole. Corresponding to the loss of transparency, many cracks and fissures were observed electron-microscopically on the surface. At the same time, a considerable increase of the surface area was found. The convex sections between the cracks and fissures can be ascribed to plastic deformation induced by the stress of transition. In spite of the remarkable changes in the surface appearance, the β-particles were unexpectedly stable on standing. The extents of the lattice disorder measured by X-ray diffractometry were found to be small. When ball-milling was applied to the β-crystals obtained by heat-induced transition, the particle size was further reduced. However, they became less stable and retransition was induced more easily at room temperature. In addition, lattice disorder attributable to the mechano-chemical effect of grinding was observed in the ground α-and β-powder.

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