Prediction of the drug release stability of different polymeric matrix tablets containing metronidazole.

The aim of the present study was to predict the structural changes of polymeric excipients in the course of storage causing undesired changes in drug release stability of tablets containing different polymers. Matrix tablets were formulated with metronidazole as a model drug, using polyvinylpyrrolidone and carbopol as matrix materials. Dissolution tests were carried out before and after storing the tablets under stress conditions for different time intervals. Parameters characterizing the release kinetics of matrix tablets, just as difference and similarity factors, were calculated to compare the release profiles as a function of storage time. FT-IR measurements were carried out to track the structural changes of the physical mixtures of metronidazole and polymers during storage. The changes of the characteristic peaks of the FT-IR spectra of metronidazole-polymer mixtures were in good correlation with the significant changes of release parameters of tablets. The latter was confirmed by ab initio calculations. The work showed that the combination of ab initio calculations with structural examinations could predict the possible instability of drug release and, thus, enables the screening of polymeric excipients of undesired physical stability.