Synthesis and Applications of Cellulose Derivatives for Drug Delivery
Marks, Joyann Audrene
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In an effort to produce new derivatives of cellulose for drug delivery applications, methods were developed to regioselectively modify C-6 halo cellulose esters to produce cationic derivatives via nucleophilic substitution. Reaction of C-6 substituted bromo and iodo cellulose with trialkylated amines and phosphines produced new cationic ammonium and phosphonium cellulose derivatives which can be explored as delivery agents for nucleic acids, proteins and other anionic drug molecules. It was anticipated that these new derivatives would not only be capable of complexing anionic drug molecules but would have greatly improved aqueous solubility compared to their precursors. The phosphonium derivatives described in this work are an obvious example of such improved solubility properties. Given the importance of cellulose derivatives in making amorphous dispersions with critical drugs, it has also been important to analyze commercially available polymers for the potential impact in oral drug delivery formulations. To do so pairwise blends of cellulosics and synthetic polymers commonly used as excipients were tested for miscibility using techniques such as DSC, mDSC, FTIR and film clarity. Miscible combinations highlight the potential to use combinations of polymers currently available commercially to provide drug delivery solutions for specific drug formulations. The use of melt extrusion in processing some of these drug/polymer dispersions provides a means of highlighting the capability for the use of these cellulosics in melt extruded amorphous dispersions. This solvent free, high pressure method significantly reduces cost and time and can be applied on a large scale. The analysis of long chain cellulose esters and ultimately the novel omega carboxy esters for melt processability significantly impacts the possibilities available for use of those excellent drug delivery agents on a much larger scale.
- Doctoral Dissertations