Physical and Chemical Changes of Medicinals in Mixtures with Adsorbents in the Solid State. I. Effect of Vapor Pressure of the Medicinals on Changes in Crystalline Properties

Abstract

It was found that some organic crystalline medicinals such as aspirin and phenacetin, when mixed with an adsorbent, gradually become amorphous during storage at room temperature (25 °C). Concomitantly, they show different dissolution patterns and decreased chemical stability. The following observations suggest that this phenomenon takes place via the gaseous phase, induced by the vapor pressure of the medicinals themselves. (1) Subliming crystals such as naphthalene become amorphous immediately in mixtures with adsorbents. (2) The rate of change of medicinals to the amorphous state is accelerated under reduced pressure in these systems. (3) The rate of change of the crystals to the amorphous state increases with their vapor pressure. The technique of treating crystalline medicinals at reduced pressure with an adsorbent may be a useful method of obtaining medicinals in the amorphous state without employing either solvents or excessive thermal or mechanical energy. © 1986, The Pharmaceutical Society of Japan. All rights reserved.