Proposal Number: 0553659 Principal Investigator: Shine, Annette D. Affiliation: University of Delaware Proposal Title: Rational Design of Biodegradable Polymer Particles Using Carbon Dioxide
Intellectual Merit In this proposed research, a rational design methodology is developed for a process to produce fine biodegradable polymeric particles suitable for pulmonary drug delivery applications. The process, termed PLUSS (Polymer Liquefaction Using Supercritical Solvation, uses compressed carbon dioxide to liquefy the polymer, followed by rapid depressurization to precipitate the polymer, free of residual solvents. In a significant departure from previous modeling, this work postulates that the morphology of precipitated polymers is governed primarily by two-phase flow hydrodynamics. The variety of experimentally observed particulate morphologies (spheres, porous irregular-shaped particles, fibers, etc.) is attributed to the solidification of the polymer in different regions of the two-phase flow map (e.g., dispersed droplet, annular, or slug flow). The PLUSS process will be examined using both experiments and process modeling. Modeling will use the assumption of homogeneous equilibrium between polymer-rich and pure CO2 phases. The objective of the modeling is to identify the structure of the phase-separated fluid at the point of polymer solidification, by mapping process conditions onto a suitable two-phase flow diagram. An experimental PLUSS apparatus will be constructed which allows independent control of the component fluxes and CO2 density, with depressurization occurring across a capillary. Particle morphology, size distribution and porosity will be determined experimentally for crystalline (polycaprolactone, polyethylene glycol) and amorphous poly(lactic-co-glycolic acid) polymers of interest in pharmaceutical applications, and comparisons made with property predictions from the two-phase PLUSS modeling. Where necessary, viscosity, melting point (or glass transition) depression and interfacial tension will be determined so that reliable model predictions can be made. If successful, this combination of experimental and modeling work will enable, for the first time, the rational design of particles using supercritical CO2 processing. If the hypothesis of two-phase flow dominance is confirmed, then innovative equipment designs are suggested, such as elbows to enhance secondary flows and promote smaller particles. A major outcome of the project will be unifying the description of supercritical fluid particle formation processes through the quantitative application of two-phase flow hydrodynamics.
Broader Impacts Broader impacts of the project include the potential for application in drug delivery together with the development of future scientists and engineers through its training of undergraduate and graduate student researchers, and through its outreach to secondary school students and teachers. High school science teachers will perform summer research to develop an inexpensive, student-friendly version of the viscosity-measurement system that can be replicated in other classrooms. Using this equipment, students can be directly and collaboratively involved in the acquisition of research data relevant to development of a glucose monitor for diabetics, while simultaneously meeting state science curriculum standards, and having fun with
