Physicochemical investigations of dipolar aprotic solvents as potential cholelitholytic agents

A number of dipolar aprotic solvents have been examined as potential co-solvents for gallstone dissolution. The power of these agents to solubilize such gallstone components as cholesterol, calcium carbonate, calcium palmitate and palmitic acid was determined and compared with that of monooctanoin (Capmul), using the synthetic solubility method. The solubilities of cholesterol and palmitic acid were greater in the N-methyl, N-ethyl and N-butylpyrrolidone derivatives than in monooctanoin. In contrast, the solubilities of the calcium salts were very low (less than 0.25% w/w) in all solvents examined. The influence of N-methylpyrrolidone (NMP) on both the in-vitro dissolution of cholesterol from gallstones and the decrease in stone weight with time was determined. NMP proved to be a better solvent than monooctanoin for human stones. NMP, which is miscible with water and monooctanoin, may have potential as a co-solvent in the design of solvent systems for gallstones.