A decreased particle size in these drug-excipient systems was confirmed by differential thermal analysis data; in most cases, a 2-3" depression in the melting point was observed. Hydrogen bonding in a gel matrix was apparently responsible for the formation of a metastable configuration in two systems: indomethacin and probucol. The polymorphic forms were first detected by differential thermal analysis and confirmed by X-ray and IR data. The existence of multiphase solids was a consequence of the presence of fumed silicon dioxide acting as a nucleating agent for the metastable crystals. Although the dissolution rates of the isolated polymorphs were found to be identical t o those of the original compounds, it is quite possible that in the dispersed state the metastable form dissolved at a rate faster than the stable form.
Since drug-excipient interactions d o readily occur in normal manufacturing procedures, and since these interactions not only alter the physical and chemical properties of the drug but also appreciably affect the physiological availability of the drug from the dosage form, it is highly desirable that such interactions be considered as a part of strict in-process quality control.