RESUMO
There is a possibility of in-situ physicochemical interactions between concomitantly administered drugs. This study aimed to investigate such physicochemical interactions between pioglitazone and rifampicin. Pioglitazone exhibited significantly higher dissolution in the presence of rifampicin, while the dissolution of rifampicin remained unaffected. The solid-state characterization of precipitates recovered after pH-shift dissolution experiments revealed the conversion of pioglitazone into an amorphous form in the presence of rifampicin. The Density Function Theory (DFT) calculations showed the intermolecular hydrogen bonding between rifampicin and pioglitazone. In-situ conversion of pioglitazone in amorphous form and subsequent supersaturation of GIT milieu translated into significantly higher in-vivo exposure of pioglitazone and its metabolites (M-III and M-IV) in Wistar rats. Therefore, it is advisable to consider the possibility of physicochemical interactions between concomitantly administered drugs. Our findings may be beneficial in tailoring the dose of concomitantly administered drugs, particularly for chronic conditions that entail polypharmacy.
