Development of high-solubility amorphous sulfasalazine: effect of hydrogen bonding

Sulphasalazine (Sulf) is a class IV compound with low aqueous solubility and low permeability which limit its therapeutic activity. This work aims to apply choline chloride (CC) and choline hydroxide (CH) as a hydrogen bond acceptor with Sulf for the production of Sulf salt. New compounds were prepared and characterized by XRD, DSC, and FT-IR. Drug solubility was evaluated in different media including pure water, and buffer pH 1.2, 4.5, and 6.8 were evaluated. The diffractogram pattern of the Sulf-CH shows a smooth and low-intensity diffraction which may indicate amorphization of the drug molecule. The FT-IR spectra confirm participation of the carboxyl group of Sulf in the formation of hydrogen bonding between Sulf and CH through salt formation which helps to enhance drug solubility. Solubility of Sulf-CH significantly increased up to 10,000-folds in pure water. Sulf-CC caused up to 2-folds enhancement in drug solubility. The difference in the solubility of Sulf-CC and Sulf-CH may suggest that each of these compounds involve different intermolecular interactions which were also confirmed by FT-IR, XRD, and DSC results. This effect can influence drug bioavailability and enhance its therapeutic efficacy.