Date of Thesis
Masters Thesis (Bucknell Access Only)
Master of Science in Chemical Engineering
Ryan C. Snyder
Amorphous dispersion, Polymorph, Vibrating orifice aerosol generator, Excipient
Particle products are important in many industries with specific current relevance to the pharmaceutical industry. In the pharmaceutical industry, the in vivo performance of an active ingredient is becoming increasingly challenging. As active ingredients are becoming more complex, they feature decreasing solubility and bioavailability. Bioavailability is affected by a number of particle properties including particle size, particle morphology, and most dramatically particle structure. Improved bioavailability due to structural changes is a product of the formation of metastable polymorphs or amorphous phases. This thesis will investigate the use of polymer excipients for the formation of metastable organic structures with the goal of improved understanding of conditions and compositional effects surrounding the formation of metastable and amorphous phases. This is performed with molecules that have a high propensity to crystallize and also includes a consideration of particle morphology. In this investigation, particles are created using a vibrating orifice aerosol generator (VOAG) to take advantage of rapid drying conditions. Experimental results show that the produced structure is strongly dependent on relative composition of the initial solution. Addition of small amounts (as low as 10 wt%) of PVP leads to production of metastable crystal structures in succinic acid from isopropanol solutions, while large PVP relative compositions (above 68.75 wt%) were able to produce purely amorphous dispersions. Variation of solvent from isopropanol did not produce structural differences; however, variations in morphology were observed. Furthermore, variations in molecular weight of the polymer excipient did not affect structure or morphology of the particles.
Webster, Luke Philip, "Formation of Metastable Organic Structures Via Monodisperse Droplet Evaporation" (2014). Master’s Theses. 124.