Effects of Solvents, Surfactants, and Complexing Agents on Stability

Effects of Solvents, Surfactants, and Complexing Agents on Stability 

Ni et al. (2002) studied the stability of SarCNU (NSC 364432) in water, ethanol, propylene glycol (PG), Capmul PG, and DMSO, as well as their combinations over the temperature range of 25-660. The two cosolvents are an 80% PG 20% ethanol mixture (PE), and a semiaqueous vehicle (WPE) containing 50% water 40% PG 10% ethanol. The degradation mechanism in all the studied solvents is the same, and the stabilization by these vehicles follows the order of Capmul PG Ethanol PE PE PG WPE water, which is in agreement with their decreasing polarities. 

Oxidative degradation is as important as hydrolysis in the stability evaluation of new drug substances. The oxygen concentration in solution is a factor in many cases and often depends upon the solvent employed. It was reported that ascorbic acid is more stable in 90% propylene glycol or in Syrup USP than in water, presumably because of the lower oxygen concentration in these vehicles (Ravin and Radebaugh, 1990). 

Effect of surfactants on stability. Many organic reactions have been found to be accelerated or inhibited in the presence of micellar media. The apparent reaction rates are altered in micellar solutions because of the distribution of substrate between the micellar and aqueous bulk phases in which different reaction rates occur (Fendler and Fendler, 1975). 

The effect of micelles on organic reactions can be attributed to both electrostatic and hydrophobic interactions (Rosen, 1979). Electrostatic interaction is important because it may affect the transition state of a reaction orthe concentration of reactant in the vicinity ofthe reaction site. The hydrophobic interactions are important because they determine the extent and the locus of solubilization in the micelle. 

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