Date of Graduation
Master of Science in Chemistry
G. Alan Schick
rheology, dynamic light scattering, Soluplus®, thermoresponsive, block copolymer, active pharmaceutical ingredient, viscosity, refractive index, thermothickening, polymeric micelles
Physical Chemistry | Polymer Chemistry
Many active pharmaceutical ingredients (APIs) are poorly soluble and cause inadequate drug absorption. Soluplus®, a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, is a commercial excipient (BASF Corp) that enhances the solubility and bioavailability of many APIs. The mechanism of enhancement is related to the ability to form polymeric micelles in solution. These micelles store insoluble APIs in their hydrophobic interior and transport them to targeted sites in the body. An important characteristic of solubility enhancers is the particle size exhibited in solution before and after loading with APIs. This is most commonly determined by dynamic light scattering (DLS) methods. However, DLS measurements involving thermothickening polymer solutions can be complicated by the temperature dependence of viscosity and refractive index, solution properties that directly impact the size analysis algorithms in DLS. In this project, the temperature dependence of viscosity for Soluplus® solutions were evaluated and used as a correction to particle size measurements by DLS. Solution concentrations ranging 1.0% to 30.0% (w/w) of Soluplus® were studied from 5.0 °C to 40.0 °C using a cone-and-plate rheometer. Refractive index of Soluplus® solutions were also studied and used in the correction of particle size. It was found that correcting viscosity and refractive index data drastically affected hydrodynamic effective diameter, where viscosity was more highly weighted. The corrected particle size of Soluplus® solutions was inversely proportional to concentration with the 0.1% and 10.0% solutions showing effective diameters of 63.13 ± 0.76 nm and 24.98 ± 0.30 nm at 25.0 °C, respectively. By properly accounting for these variables in DLS algorithms, particle size of thermoresponsive polymer solutions can be more accurately characterized.
© Jessica Diane Bruer
Bruer, Jessica Diane, "Determining Particle Size of Polymeric Micelles in Thermothickening Aqueous Solutions" (2020). MSU Graduate Theses. 3472.