Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Physical and Chemical Changes of Medicinals in Mixtures with Adsorbents in the Solid State. II. : Application of Reduced Pressure Treatment for the Improvement of Dissolution of Flufenamic Acid
Tsutomu KONNOKoji KINUNO
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JOURNAL FREE ACCESS

1989 Volume 37 Issue 9 Pages 2481-2484

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Abstract

Flufenamic acid (FFA) was mixed with magnesium aluminum silicate (MAS) and stored at 60°C at a reduced pressure of about 2.5 mmHg. After storage, when its concentration was not more than 20%, FFA was observed by X-ray diffraction and polarizing microscopy to be amorphous. The dissolution of FFA was thus enhanced in comparison with that of a freshly prepared mixture. Furthermore, the dissolution curves showed a typical supersaturation pattern, and the supersaturation state continued longer, the higher the pH value of the dissolution medium. Flufenamic acid, in a mixture with MAS, became amorphous more rapidly at reduced pressure than at atmospheric pressure, and therefore the effect improved dissolution appeared earlier at reduced pressure. Infrared spectral studies suggested that FFA, after storage at a reduced pressure with MAS, was dispersed monomolecularly in an ionic form. The technique of treating crystalline medicinals, that have poor solubility in water, with adsorbent at reduced pressure may be useful for improving their dissolution characteristics.

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© The Pharmaceutical Society of Japan
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