Synthesis and characterization of neutral and anionic cellulosic amphiphiles

Polymer design and selection are crucial to the development of amorphous solid dispersions (ASD) for solubilization of otherwise poorly water-soluble drugs. The matrix polymer is required to interact strongly at the molecular level with the drug to prevent recrystallization, but must also be able to release the drug at an adequate rate upon entering the absorptive portion of the digestive tract. Herein we report versatile syntheses of a non-ionic, water-soluble cellulosic polymer family, cellulose trioxodecanoates, containing a hydrophilic oligo(ethylene oxide) side chain. This series of cellulose derivatives is designed for both adequate stabilization of amorphous drugs with high crystallization tendency, and timely release of those drugs. Alternatively, these polymers can be rendered anionic by also appending a pH-responsive ω-carboxyalkanoate group. Detailed structural information and structure–property relationship characterization of these amphiphilic polymers are described, which will permit evaluation of these materials as ASD polymers for enhancement of drug solubility and bioavailability.