Factors affecting the chemical stability of carboxylic acid drugs in Enhanced Solubility System (ESS) Softgel Formulations Based on Polyethylene Glycol (PEG).

Abstract

Drug decomposition in ESS softgel formulations of three monocarboxylic acid drugs was measured after accelerated storage of solutions at 105 deg C for 3 or 7 days. Drug decompostion occured primarily by reaction between the unionised carboxylic acid function of the drug and the alcoholic groupings of the components in the solvent (e.g. PEG, glycerin) to form mainly the corresponding mono-esters. The ionised form of the drug was relatively unreactive. Different solvents were evaluated and the corresponding drug decomposition rates were explained in terms of the alcoholic group content of the solvent components. The presence of water in the formulation decreased the reaction rate. A rate equation was derived and utilised to compare chemical stabilities of related formulations. The stabilities of similar ESS formulations of the three drugs were greatly different due to differences in the intrinsic reactivities of the drugs The findings of this study can be used to maximise chemical stability of ESS formulations of carboxylic acid drugs.