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Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Chemical Engineering

Year Degree Awarded

2015

Month Degree Awarded

February

First Advisor

Michael A. Henson

Subject Categories

Food Processing | Other Chemical Engineering | Process Control and Systems

Abstract

This thesis presents both experimental and modeling studies on the formulation of stable lipid nanoparticle dispersions. A population balance equation (PBE) model was developed for prediction of the average polymorph content and aggregate size distribution to better understand the undesirable SLN aggregation behavior. Experimental and modeling studies showed that the polymorphic transformation was the rate determining step for my system, SLNs with smaller initial size distributions aggregated more rapidly, and aggregates contained particles with both alpha and beta crystals. Next the effect of different liquid carrier oils on the crystallization and aggregation behavior of tristearin NLC dispersions was investigated. I found that NLC dispersion stability was strongly affected by the type and amount of the oil. The results suggested that oil trapped within the growing crystal matrix accelerated the polymorphic transformation but retarded the large shape change normally associated with the transformation. Based on PBE simulation results, I hypothesized that improved NLC dispersion stability was attributable to both reduced particle shape change, which created less new surface area to be covered by surfactant, and increased mobility of surfactant molecules, which resulted in available surfactant being more efficient at covering created surface area. Finally I also studied the effect of formulation variables on the aggregation behavior and rheology of NLC dispersions. I found that NLC dispersion viscosity was strongly affected by particle aggregation. The viscosity of the dispersion could be modified by at least an order of magnitude by controlling particle aggregation using different surfactant and oil concentrations. Oscillatory sweep tests showed typical behaviors of a viscoelastic liquid and a viscoelastic solid for non-aggregated and aggregated NLC dispersions, respectively. Modeling results suggested a stronger bonding force and a higher aggregation efficiency with decreasing surfactant and/or oil concentrations. Both oscillatory sweep experiments and modeling results indicated an interconnected network structure in the aggregated dispersions, while no indication of network formation was observed for non-aggregated dispersions. These results suggested that controlled aggregation represents a promising approach for modifying the viscosity of NLC dispersions without adding viscosity enhancers and could reduce the time and cost for NLC production.

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