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.

药物的水溶性差，助长了复杂的配方，并危及患者获得药物的机会。为简化这些复杂性，我们系统地合成了36种空间需求抗衡离子的文库，并绘制了Selurampanel（一种难于治疗偏头痛的水溶性差的药物）的无定形离子液体策略的药物设计空间。口服给药后减轻的偏头痛症状将使患者受益。因此，我们对离子液体的通量，过饱和期和吸湿性进行了研究，从而得出了将分子抗衡离子描述符与药物预测结果联系起来的算法。通过这种方式，过饱和时间和通量可提高30或800倍，这是通过结构抗衡离子对持续释放曲线的即时响应 与Selurampanel的结晶游离酸相比，优化效果最佳。以离子液体结构为指导，体内分布范围从快速的生物利用度和高的最大血浆浓度到持续的模式。总之，该研究概述并预测了基于无定形离子液体和无赋形剂的制剂的可达到的药物设计空间，指出了离子液体设计的巨大药学潜力。