Most drugs in development and on the market have limitations because they are very lipophilic and tend to crystallize rapidly out of aqueous solutions, thereby causing poor oral bioavailability in vivo. Consequently, although a drug may have high therapeutic efficacy to treat severe diseases (e.g. cancer and HIV), it cannot come to market and reach patients in need. To improve drug solubility and bioavailability, thereby enhancing the chances that these medicines become viable treatments for ill patients, research into amorphous solid dispersions (ASDs) as oral-delivery drug carriers has garnered much attention from academia and the pharmaceutical industry. High-performing ASD polymers often have high Tg, carboxyl groups, sufficient hydrophobicity, and good water solubility. Recently, our research has focused on functionalizing α-1,3-glucan polymers to create novel ASD polymers, then evaluating the impact of polymer morphology on ASD performance. α-1,3-Glucans have identical polarity relative to cellulose (β-1,4-glucans); however, their structures differ from that of cellulose due to their α-1-&gt;3 linkages which incorporate kinks in the polymer chain, significantly changing secondary structure and solubility. In this work we report the synthesis of α-1,3-glucan acetyl and propionyl derivatives of varying degrees of substitution, then esterifying the modified backbones with succinic or glutaric anhydride to create polymer libraries of novel glucan derivatives. Polymers were characterized by NMR, TGA, and GPC. Then evaluated as potential ASD polymers with several candidate drugs to determine their efficacy as crystallization inhibitors. Inhibitory power was then compared to that of cellulose ester polymers previously synthesized by the Edgar group to determine whether and how the morphology of these polysaccharides affects drug crystallization inhibition.

Synthesis of α-1,3-glucan esters for amorphous solid dispersion technologies: Impact of morphology on performance

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