Optimization of pH and Paraben Concentration in a Non-Aqueous Solution Formulation with Transesterification Reaction Products of Parabens (alkyl -4-hydroxybenzoates) and Glycerin

The formation of trans-esterification byproducts of methyl- and propylparaben with glycerin was observed during formulation of an oral solution drug product. To obtain a stable product that is physically, chemically and microbial stable during storage at room temperature conditions, the pH of the formulation and the concentration level of the parabens were optimized meticulously to obtain a robust manufacturing process. An HPLC method was developed and fully validated for the determination of methyl- and propylparaben in the formulation. The method was able to detect the levels of the transesterifcation byproducts as well. Typical validation parameters such as accuracy, precision, and linearity, etc. were assessed, along with demonstration of the robustness, stability of solution, evaluation of forced degradation studies and setting of system suitability tests and criteria.