This study focused on the physicochemical interactions between acidic and basic drugs in aqueous solutions. Their ion pair interactions were evaluated in an in vitro study. The model non-steroid anti-inflammatory drugs (NSAIDs), indomethacin (INM) and diclofenac (DIC), were used as acidic and hydrophobic drugs, whereas cimetidine (CIM), famotidine (FAM), and imidazole (IMD) were used as basic additives with heterocyclic moieties. The drug mixtures were evaluated by thermal analysis, dissolution test, nuclear magnetic resonance (NMR) spectroscopy, and mass spectroscopy. The fusion enthalpy of DIC-CIM, INM-CIM, and INM-arginine (ARG) sample was calculated based on melting temperature transformation. The DIC mixture with CIM, IMD, antipyrine (ANT), and ARG showed enhanced solubility, whereas the DIC-FAM mixture sample showed a decreased solubility. Electrospray ionization mass spectroscopy was carried out to detect binary mixtures. The interactions in DIC-FAM mixture sample were found between the carboxyl group of DIC and the amine groups of FAM by NMR. These findings were suggested that DIC-FAM mixture samples construct ion pair complexes based on the theory of Bjerrum. Moreover, the acid model drug and basic model drug also can be constructed 1:1 complexes that affects their solubility in the solvent of water type.
Keywords: Anisotropic effect; Complexation; Ion pair; Non-steroid anti-inflammatory; Solubility.
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