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Abstract
Blends of hydroxypropyl methylcellulose acetate succinate (HPMCAS) and dodecyl (C12)-tailed poly(N-isopropylacrylamide) (PNIPAm) were systematically explored as a model system to dispense the active ingredient phenytoin by rapid dissolution, followed by the suppression of drug crystallization for an extended period. Dynamic and static light scattering revealed that C12-PNIPAm polymers, synthesized by reversible addition-fragmentation chain-transfer polymerization, self-assembled into micelles with dodecyl cores in phosphate-buffered saline (PBS, pH 6.5). A synergistic effect on drug supersaturation was documented during in vitro dissolution tests by varying the blending ratio, with HPMACS primarily aiding in rapid dissolution and PNIPAm maintaining supersaturation. Polarized light and cryogenic transmission electron microscopy experiments revealed that C12-PNIPAm micelles maintain drug supersaturation by inhibiting both crystal nucleation and growth. Cross-peaks between the phenyl group of phenytoin and the isopropyl group of C12-PNIPAm in 2D 1H nuclear Overhauser effect (NOESY) spectra confirmed the existence of drug-polymer intermolecular interactions in solution. Phenytoin and polymer diffusion coefficients, measured by diffusion-ordered NMR spectroscopy (DOSY), demonstrated that the drug-polymer association constant increased with increasing local density of the corona chains, coincident with a reduction in C12-PNIPAm molecular weight. These findings demonstrate a new strategy for exploiting the versatility of polymer blends through the use of self-assembled micelles in the design of advanced excipients.
Original language | English (US) |
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Pages (from-to) | 2837-2848 |
Number of pages | 12 |
Journal | Langmuir |
Volume | 33 |
Issue number | 11 |
DOIs | |
State | Published - Mar 21 2017 |
Bibliographical note
Publisher Copyright:© 2017 American Chemical Society.
How much support was provided by MRSEC?
- Shared
Reporting period for MRSEC
- Period 3
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
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MRSEC IRG-3: Hierarchical Multifunctional Macromolecular Materials
Reineke, T. M., Bates, F. S., Dorfman, K., Dutcher, C. S., Hillmyer, M. A., Lodge, T., Morse, D. C., Siepmann, I., Barreda, L. & Ganewatta, M. S.
1/1/98 → …
Project: Research project
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