Amphiphilic hydroxyalkyl cellulose derivatives for amorphous solid dispersion prepared by olefin cross-metathesis. Issue 30 (13th July 2016)

• Record Type: Journal Article
• Authors: Dong, Yifan; Mosquera-Giraldo, Laura I.; Troutman, Jacob; Skogstad, Brittny; Taylor, Lynne S.; Edgar, Kevin J.
• Is Part Of: Polymer chemistry. Volume 7:Issue 30(2016)
• Page Start: 4953
• Page End: 4963
• Publication Date: 2016-07-13
• Subjects: Polymers -- Periodicals; Macromolecules -- Periodicals; Polymerization -- Periodicals; 547.705
• DOI: 10.1039/c6py00960c
• Languages: English
• ISSNs: 1759-9954

Abstract

Abstract : Olefin CM followed by transfer hydrogenation is an efficient method for synthesizing amphiphilic hydroxypropyl cellulose derivatives. Abstract : Olefin cross-metathesis (CM) has enabled design and synthesis of diverse, amphiphilic cellulose ether derivatives ( e.g. of ethyl and methyl cellulose). In this paper, hydroxyalkyl cellulose was selected as a hydrophilic starting material, with the additional advantage that it has DS (OH) 3.0 that allows targeting of a full range of DS of selected functional groups. Hydroxypropyl cellulose (HPC) was first etherified with 5-bromopent-1-ene to attach olefin "handles" for metathesis, whereby control of molar ratios of sodium hydride and 5-bromopent-1-ene permits full DS control of appended olefin. These olefin-terminated HPC ethers then were subjected to CM with acrylic acid and different acrylates, followed by diimide hydrogenation to reduce the resulting α, β-unsaturation. NMR and FT-IR spectroscopies were useful tools for following reaction progress. One of the product carboxyl-functionalized HPC derivatives, designated HPC-Pen106-AA-H, showed high promise as a crystallization inhibitor of the antiviral drug telaprevir. Its nucleation-induction inhibitory ability was compared to those of commercial controls, HPC and HPMCAS. All three polymers were very effective for inhibiting telaprevir crystallization, increasing induction time up to 8-fold. HPC did not effectively prevent amorphous particle growth, whereas the carboxyl-containing HPC-Pen106-AA-H and HPMCAS were able to prevent formation of agglomerates of amorphous drugs.