Abstract：
Iloperidone (ILO) is a poorly soluble and bioavailable WHO-approved schizophrenia drug. Microneedles are a revolutionary delivery technology that overcomes many of the issues associated with traditional drug administration. The current research aimed to compare the antipsychotic activity and pharmacokinetics of ILO-loaded dissolving microneedles (DMNs) and transdermal film with a solid microneedle (STF). The DMNs were fabricated using the micromolding process, while the transdermal film was created using the solvent casting approach. Furthermore, an in vivo pharmacokinetic, pharmacodynamic, and skin irritation study was performed on Wistar rats. Studies were compared with transdermal film (TF) on untreated skin as a passive control. STF and DMNs had considerably greater AUC and Cmax (p ≤ 0.001) than transdermal film. In pharmacodynamic tests, STF and DMNs demonstrated significant (p ≤ 0.001) forelimb retraction time (FRT) and hindlimb retraction time (HRT) delay responses as compared to control and TF. In the skin irritation test, no adverse effects such as erythema or edema were observed at the end of the 48 h. Thus, antipsychotic activity (paw test) and pharmacokinetics studies revealed sustained action of DMN and STF. This research revealed that improved efficacy of DMN and STF for antipsychotic drug delivery may be an alternative to the existing dosage form.
摘要：
Iloperidone（ILO）是一种难溶性和生物可利用性的精神分裂症药物。微针是一种革命性的递送技术，克服了与传统药物管理相关的许多问题。当前的研究旨在比较负载有ILO的溶解微针（DMNs）和经皮膜与固体微针（STF）的抗精神病活性和药代动力学。DMN是使用微成型工艺制造的，而透皮膜是使用溶剂流延方法产生的。此外，体内药代动力学，药效学，对Wistar大鼠进行皮肤刺激研究。将研究与未经处理的皮肤上的透皮膜（TF）作为被动对照进行比较。STF和DMNs的AUC和Cmax（p≤0.001）明显高于透皮膜。在药效学试验中,与对照组和TF相比，STF和DMNs显示出显着（p≤0.001）的前肢回缩时间（FRT）和后肢回缩时间（HRT）延迟反应。在皮肤刺激试验中,在48小时结束时没有观察到红斑或水肿等不良反应。抗精神病活性（爪试验）和药代动力学研究显示DMN和STF的持续作用。这项研究表明，改善DMN和STF用于抗精神病药物递送的功效可能是现有剂型的替代方案。
