Surface-Modified Cellulose Nanocrystal Gels for Applications in Pharmaceutical Crystallization
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Oral drug delivery is the most common and preferred form of drug administration into the body, especially for small molecule active pharmaceutical ingredients (APIs). APIs often exist as different polymorphic forms with unique physical and chemical properties including crystal size, shape, and purity, which can lead to vastly different behavior in terms of stability, bioavailability, dosage, and exposure limits. Pharmaceutical crystal engineering can be used to control the polymorphic forms of drugs and in recent years, the desire for polymorph control has led to the development of several new production methods including heterogeneous crystallization from surfaces and confined crystallization within pores. Pharmaceutical crystallization in a gel network presents a system with control over both the surface chemistry, for heterogeneous crystallization from a surface, and over the gel pores for crystallization within pore. The purpose of the research in this thesis is to develop cellulose nanocrystal (CNC) based gel systems to be used as a favorable environment for crystallizing small molecule APIs. Using modified CNCs, we developed supramolecular organogel systems to crystallize a variety of sulfur-based antibiotics with multiple polymorphs. Additionally, we developed an aerogel system for crystallizing and stabilizing pharmaceuticals with metastable polymorphs and finally surface modified CNC aerogels were used to show the combined effects of surface templating and confinement for directing polymorphism of a model pharmaceutical intermediate. The results from this work provide an avenue towards using CNCs in pharmaceutical engineering to shift towards polymorphs with higher water solubility or to forms with more sustained release behavior to increase the duration for drug uptake into the body, while reducing the total required dosage of the drug.