Crystalline palmatine saccharinate pharmaceutical salt without reducing solubility and improving its hygroscopic stability with regard to palmatine chloride

Abstract

In order to improve the hygroscopic stability of palmatine chloride (PMTCl) without reducing its solubility, on the basis of summarizing tetrahydroberberine and sulfophenyl acids pharmaceutical cocrystals/salts, we speculated that sodium saccharinate (SACNa), an organic acid salt with the same sulfonyl group, may be cocrystallized with ionic PMT. Consequently, an unreported PMT-SAC (C21H22NO4·C7H4NO3S) pharmaceutical salt was synthesized. The maximum solubility of PMT-SAC in pure water is essentially the same as that of PMTCl. As the hygroscopic stability of PMT-SAC is significantly improved, it is speculated that in the PMT-SAC pharmaceutical salt, PMT cations and SAC anions mainly rely on hydrogen bonds to accumulate, due to the fact that the hydrogen bonds acting between the groups of PMT cations and SAC anions are nearly saturated, it is therefore difficult for PMT cations to combine with external water molecules. This implies that a single crystal of pharmaceutical salt with the desired physicochemical properties will conceivably be obtained for ionic active pharmaceutical ingredients through the introduction of organic acid salts, which are able to form hydrogen bonds. Further to this, it is of note that the antibacterial activities in vitro of a pharmaceutical salt of PMT-SAC is improved, when compared with the corresponding parent compound (PMTCl).