%0 Journal Article
%T Threading the needle: Achieving simplicity and performance in cellulose alkanoate ω-carboxyalkanoates for amorphous solid dispersion.
%A Petrova SP
%A Mohamed MA
%A Wu H
%A Taylor LS
%A Edgar KJ
%J Carbohydr Polym
%V 333
%N 0
%D 2024 Jun 1
%M 38494207
%F 10.723
%R 10.1016/j.carbpol.2024.121988
%X Most active pharmaceutical ingredients (APIs) suffer from poor water solubility, often keeping them from reaching patients. To overcome the issues of poor drug solubility and subsequent low bioavailability, amorphous solid dispersions (ASDs) have garnered much attention. Cellulose ester derivatives are of interest for ASD applications as they are benign, sustainable-based, and successful in commercial drug delivery systems, e.g. in osmotic pump systems and as commercial ASD polymers. Synthesis of carboxy-pendant cellulose esters is a challenge, due in part to competing reactions between carboxyls and hydroxyls, forming ester crosslinks. Herein we demonstrate proof-of-concept for a scalable synthetic route to simple, yet highly promising ASD polymers by esterifying cellulose polymers through ring-opening of cyclic succinic or glutaric anhydride. We describe the complexity of such ring-opening reactions, not previously well-described, and report ways to avoid gelation. We report synthesis, characterization, and preliminary in vitro ASD evaluations of fifteen such derivatives. Synthetic routes were designed to accommodate these criteria: no protecting groups, no metal catalysts, mild conditions with standard reagents, simple purification, and one-pot synthesis. Finally, these designed ASD polymers included members that maintained fast-crystallizing felodipine in solution and release it from an ASD at rather high 20 % drug loading (DL).