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Mapping the pharmaceutical design space by amorphous ionic liquid strategies.

Journal of controlled release : official journal of the Controlled Release Society (2017-11-04)
Johannes Wiest, Marco Saedtler, Anja Balk, Benjamin Merget, Toni Widmer, Heike Bruhn, Marc Raccuglia, Elbast Walid, Franck Picard, Helga Stopper, Wolfgang Dekant, Tessa Lühmann, Christoph Sotriffer, Bruno Galli, Ulrike Holzgrabe, Lorenz Meinel

Poor water solubility of drugs fuels complex formulations and jeopardizes patient access to medication. Simplifying these complexities we systematically synthesized a library of 36 sterically demanding counterions and mapped the pharmaceutical design space for amorphous ionic liquid strategies for Selurampanel, a poorly water soluble drug used against migraine. Patients would benefit from a rapid uptake after oral administration to alleviate migraine symptoms. Therefore, we probed the ionic liquids for the flux, supersaturation period and hygroscopicity leading to algorithms linking molecular counterion descriptors to predicted pharmaceutical outcome. By that, 30- or 800-fold improvements of the supersaturation period and fluxes were achieved as were immediate to sustained release profiles through structural counterions' optimization compared to the crystalline free acid of Selurampanel. Guided by ionic liquid structure, in vivo profiles ranged from rapid bioavailability and high maximal plasma concentrations to sustained patterns. In conclusion, the study outlined and predicted the accessible pharmaceutical design space of amorphous ionic liquid based and excipient-free formulations pointing to the enormous pharmaceutical potential of ionic liquid designs.

Product Number
Product Description

Tetrabutylphosphonium hydroxide solution, 40 wt. % in H2O
Pyrvinium pamoate salt hydrate, ≥98% (HPLC)
Tripropylphosphine, 97%