419844 High-Throughput Polymer Screening for Oral Drug Delivery: From Discovery to Design

Tuesday, November 10, 2015: 8:55 AM
Ballroom D (Salt Palace Convention Center)
Jeffrey M. Ting1, Swapnil Tale2, Lakmini Widanapathirana2, Zachary P. Tolstyka2, Seamus D. Jones1, Steven Guillaudeu3, Li Guo3, Frank S. Bates1 and Theresa M. Reineke2, (1)Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN, (2)Department of Chemistry, University of Minnesota, Minneapolis, MN, (3)Formulation Science, The Dow Chemical Company, Midland, MI

Spray-dried dispersions are fascinating polymer–drug mixtures that exploit the amorphous state of a hydrophobic drug to dramatically elevate its aqueous solubility above equilibrium for oral administration. However, these materials have limited fundamental understanding of what polymeric attributes prolong drug supersaturation and combat crystallization in solution. We present an automated protocol to combinatorially explore a vast architectural parameter space for five polymer platforms and elucidate how specific microstructures dictate drug dissolution. Over 60 reversible addition-fragmentation chain transfer (RAFT) polymerizations were conducted in three high-throughput experiments, varying constituent properties such as polymer amphilicity, thermoresponsive phase behavior, and hydrogen bonding capability. The intermolecular interactions of well–defined lead compounds with model drug phenytoin were screened and studied in vitro. This study reports the first results of a polymer–focused screening assay that successfully solubilized an otherwise-intractable drug for oral delivery.

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