Lurasidone is an important antipsychotic drug indicated for the treatment of schizophrenia and bipolar disorder, with an oral bioavailability of 9–19% owing to its poor aqueous solubility. Additionally, lurasidone exhibits a 2-fold positive food effect, such that patients must administer their medication with a meal, leading to significant non-compliance. The aim of this research was to evaluate the in vitro and in vivo performance of lurasidone when engineered as nanostructured systems. Specifically, a nanosuspension, nano-emulsion and silica-lipid hybrid (SLH) microparticles were formulated and the influence of composition and nanostructure on the mechanism of solubilisation was compared. Formulations were shown to enhance fasted state solubilisation levels in vitro by up to 5.9-fold, compared to pure drug. Fed- and fasted-state solubilisation profiles revealed that in contrast to the nanosuspension and nano-emulsion, lurasidone SLH mitigated the positive pharmaceutical effect of lurasidone. In vivo pharmacokinetic evaluations revealed that the nanosuspension, nano-emulsion and SLH enhanced the bioavailability of lurasidone by 3-fold, 2.4-fold and 8.8-fold, respectively, compared to pure drug after oral administration. For lurasidone, the combination of lipid-based nanostructure and porous silica nanostructure (SLH) led to optimal fasted state bioavailability which can ultimately result in enhanced treatment efficacy, easier dosing regimens and improved patient outcomes.

Lurasidone 是一种重要的抗精神病药物，用于治疗精神分裂症和双相情感障碍，由于其水溶性较差，口服生物利用度为 9-19%。此外，鲁拉西酮表现出 2 倍的积极食物效应，因此患者必须随餐服用药物，从而导致严重的不依从性。本研究的目的是评估鲁拉西酮在设计为纳米结构系统时的体外和体内性能。具体而言，配制了纳米混悬液、纳米乳液和二氧化硅-脂质杂化 (SLH) 微粒，并比较了组成和纳米结构对增溶机制的影响。已证明制剂可提高体外禁食状态的溶解水平与纯药物相比，最高可达 5.9 倍。进食和禁食状态的增溶曲线显示，与纳米混悬剂和纳米乳剂相比，鲁拉西酮 SLH 减轻了鲁拉西酮的积极药效。体内 p危害动力学评估显示，与口服纯药物相比，纳米混悬液、纳米乳剂和 SLH 分别使 lurasidone 的生物利用度提高了 3 倍、2.4 倍和 8.8 倍。对于鲁拉西酮，基于脂质的纳米结构和多孔二氧化硅纳米结构 (SLH) 的组合导致最佳的禁食状态生物利用度，最终可以提高治疗效果，更容易给药方案并改善患者预后。