Threading the needle: Achieving simplicity and performance in cellulose alkanoate ω-carboxyalkanoates for amorphous...

Area of Science:

• Polymer Chemistry
• Materials Science
• Pharmaceutical Sciences

Background:

• Many active pharmaceutical ingredients (APIs) exhibit poor water solubility, limiting their therapeutic efficacy.
• Amorphous solid dispersions (ASDs) are a key strategy to enhance the solubility and bioavailability of such APIs.
• Cellulose ester derivatives offer a sustainable and biocompatible platform for ASDs, with existing commercial applications.

Purpose of the Study:

• To develop a scalable and efficient synthetic route for carboxy-pendant cellulose ester polymers for ASD applications.
• To investigate and overcome challenges in synthesizing these polymers, such as preventing ester crosslinking and gelation.
• To evaluate the potential of these novel polymers in improving the dissolution of poorly soluble drugs.

Main Methods:

• Esterification of cellulose using ring-opening of cyclic succinic or glutaric anhydride under mild, catalyst-free conditions.
• Synthesis of fifteen novel cellulose ester derivatives via a one-pot procedure without protecting groups.
• Characterization of synthesized polymers and in vitro evaluation of amorphous solid dispersions (ASDs) with felodipine.

Main Results:

• A scalable synthetic route was established for carboxy-pendant cellulose esters, avoiding gelation and complex purification.
• Fifteen novel cellulose ester derivatives were successfully synthesized and characterized.
• The developed ASD polymers effectively maintained felodipine in solution and facilitated its release at a 20% drug loading.

Conclusions:

• The novel synthetic approach provides a promising pathway to produce advanced cellulose ester-based polymers for amorphous solid dispersions.
• These polymers demonstrate significant potential for enhancing the delivery of poorly water-soluble drugs, addressing a critical challenge in pharmaceutical development.
• The study highlights the versatility of cellulose derivatives in creating effective drug delivery systems.