VTechWorks staff will be away for the Thanksgiving holiday starting Wednesday afternoon, Nov. 25, through Sunday Nov. 29, and will not be replying to requests during this time. Thank you for your patience.
Amphiphilic hydroxyalkyl cellulose derivatives for amorphous solid dispersion prepared by olefin cross-metathesis
Mosquera-Giraldo, Laura I.
Taylor, Lynne S.
Edgar, Kevin J.
MetadataShow full item record
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.