Category
JFL, Lower Atrium
Description
Pharmaceutical drugs are formulated with various substances to maintain structure, stability, and sterility. Nonionic surfactants prevent aggregation and improve stability while preservatives are used to uphold sterility against microbial contamination. Both compounds are necessary for formulations to ensure drug administration is satisfactory. While surfactants and preservatives are well soluble in water separately, when these materials are mixed even at relatively low concentrations, they become insoluble leading to detrimental aggregation in the form of observable turbidity followed by large-scale phase separation. Previous work has demonstrated that prior to the formation of unstable turbid aggregates, the preservative phenol forms micelles with the surfactant poloxamer 188. This micellization is stable in the long term, so long as the phenol concentration remains below a threshold concentration for turbidity. Here we aim to determine whether turbidity can be reversed once that threshold phenol concentration is crossed. Using a series of methods including vortex, dilution, and temperature cycling, we will explore means of reintegrating mixtures of phenol and poloxamer 188 to produce stable formulations. We will quantify success first by visual observation and subsequently by various scattering techniques, including ultraviolet-visible light spectrophotometry. Our results will provide insight into the reversibility of aggregation and phase separation and will give understanding of optimal concentrations to maximize stability and sterility of drug formulations broadly applicable across the pharmaceutical industry.
Reversibility of Aggregation and Phase Separation in P188/Preservative mixtures in Pharmaceutical Formulations
JFL, Lower Atrium
Pharmaceutical drugs are formulated with various substances to maintain structure, stability, and sterility. Nonionic surfactants prevent aggregation and improve stability while preservatives are used to uphold sterility against microbial contamination. Both compounds are necessary for formulations to ensure drug administration is satisfactory. While surfactants and preservatives are well soluble in water separately, when these materials are mixed even at relatively low concentrations, they become insoluble leading to detrimental aggregation in the form of observable turbidity followed by large-scale phase separation. Previous work has demonstrated that prior to the formation of unstable turbid aggregates, the preservative phenol forms micelles with the surfactant poloxamer 188. This micellization is stable in the long term, so long as the phenol concentration remains below a threshold concentration for turbidity. Here we aim to determine whether turbidity can be reversed once that threshold phenol concentration is crossed. Using a series of methods including vortex, dilution, and temperature cycling, we will explore means of reintegrating mixtures of phenol and poloxamer 188 to produce stable formulations. We will quantify success first by visual observation and subsequently by various scattering techniques, including ultraviolet-visible light spectrophotometry. Our results will provide insight into the reversibility of aggregation and phase separation and will give understanding of optimal concentrations to maximize stability and sterility of drug formulations broadly applicable across the pharmaceutical industry.
Comments
Undergraduate