Physical and chemical changes of medicinals in mixtures with adsorbents in the solid state. IV. Study on reduced-pressure mixing for practical use of amorphous mixtures of flufenamic acid.

Abstract

Flufenamic acid (FFA) was mixed with magnesium aluminum silicate (MAS) at a reduced pressure of about 10 to 50 mmHg employing a commercial mixer for pharmaceutical production. An amorphous state of FFA in the mixture was efficiently achieved with this equipment, and the dissolution of FFA was enhanced in comparison with that of the physical mixture. Effects of the conditions of mixing, such as pressure, temperature and rotating speed, on dissolution of FFA were determined. Through stability tests at 40 degrees C under both dry and humid conditions, no change in dissolution profiles was recognized in a 5% FFA mixture stored under any conditions. On the other hand, decreases in dissolution behavior were observed in 10% and 20% FFA mixtures when they were stored under humid conditions. These results suggested that humidity should be avoided during the storage of amorphous mixtures of FFA with MAS for production purposes.