Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Effects of Grinding on Physical and Chemical Properties of Crystalline Medicinals with Microcrystalline Cellulose. I. Some Physical Properties of Crystalline Medicinals in Ground Mixtures
YOSHINOBU NAKAIEIHEI FUKUOKASHINICHIRO NAKAJIMAKEIJI YAMAMOTO
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1977 Volume 25 Issue 12 Pages 3340-3346

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Abstract
Crystalline medicinals were ground with microcrystalline cellulose by a stainless steel shaker mill. The medicinal changed in their physical properties in grinding the mixture of a 10% medicinal. X-ray reflection lines due to the medicinal decreased in their intensities with the increasing time of grinding. The intensity of characteristic lines was not observed after the 2 hr grinding and halo pattern was obtained. The heat of fusion due to the medicinals was not observed for the 2 hr ground mixture. There was the critical content of medicinals in the ground mixture to show the halo pattern on the X-ray diffractogram and no heat of fusion on the thermogram. The medicinals were released rapidly from the ground mixtures in the aqueous solution and the solution reached the saturated concentration in a very short time. These phenomena occurred in all crystalline medicinals independent of the molecular properties, such as structure, size, and polarity. The residual cellulose, the ground mixture of benzoic acid from which the acid had been released, had the large pore volume of capillaries at about 30-40 A. It was estimated that the medicinal molecules were dispersed within the cellulose as a molecule or a microassembly of the molecules having no preferred orientation. The assembly was probably isolated being enclosed by the cellulose molecules which were bound by hydrogen bond. The ground mixture may be regarded as an"entropy frozen solution, "that is, a medicinal dissolves in cellulose without the ability of molecular translation movement.
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© The Pharmaceutical Society of Japan
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