Studies on impact of co-former selection on physicochemical properties of crystalline active pharmaceutical complexes
Studies on the enhanced bioavailability profile of existing antibiotics are essential, considering growing bacterial resistance and increasing demand on cost-effective and safe antibacterial treatments.
Previous studies have indicated that it is possible to generate alternative stoichiometries of salts of dicarboxylic acids (DCAs) with amphoteric molecule of ciprofloxacin. It has been proved that salts may be stable in aqueous solution or undergo liquid mediated transformation generating a supersaturation effect in aqueous media. DCA salts have generated pharmaceutically favourable pH-solubility profiles when compared to the well-established CPR hydrochloride salt on the market. Up to date supersaturation phenomena was ascribed solely to thermodynamically unstable amorphous forms undergoing liquid mediated crystallisation, nanoparticulate domains supersaturating through Oswald ripening effect or co-crystalline forms, developing incongruent solubility profiles. Metastable in aqueous environments, organic salts are alternative of choice for all these solid-state forms due to ease of production, using established methods and equipment as well as better process-related environmental physicochemical stability.
To date, limited studies have been performed to understand intermolecular interactions governing enhanced solubility characteristics conveying on improved passive cell membrane permeability profile of drugs.