School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK; Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
Int J Pharm. 2024 Jul 20;660:124342. doi: 10.1016/j.ijpharm.2024.124342. Epub 2024 Jun 15.
Schizophrenia is a psychiatric disorder that results from abnormal levels of neurotransmitters in the brain. Risperidone (RIS) is a common drug prescribed for the treatment of schizophrenia. RIS is a hydrophobic drug that is typically administered orally or intramuscularly. Transdermal drug delivery (TDD) could potentially improve the delivery of RIS. This study focused on the development of RIS nanocrystals (NCs), for the first time, which were incorporated into dissolving microneedle array patches (DMAPs) to facilitate the drug delivery of RIS. RIS NCs were formulated via wet-media milling technique using poly(vinylalcohol) (PVA) as a stabiliser. NCs with particle size of 300 nm were produced and showed an enhanced release profile up to 80 % over 28 days. Ex vivo results showed that 1.16 ± 0.04 mg of RIS was delivered to both the receiver compartment and full-thickness skin from NCs loaded DMAPs compared to 0.75 ± 0.07 mg from bulk RIS DMAPs. In an in vivo study conducted using female Sprague Dawley rats, both RIS and its active metabolite 9-hydroxyrisperidone (9-OH-RIS) were detected in plasma samples for 5 days. In comparison with the oral group, DMAPs improved the overall pharmacokinetic profile in plasma with a ∼ 15 folds higher area under the curve (AUC) value. This work has represented the novel delivery of the antipsychotic drug, RIS, through microneedles. It also offers substantial evidence to support the broader application of MAPs for the transdermal delivery of poorly water-soluble drugs.
精神分裂症是一种由大脑中神经递质水平异常引起的精神疾病。利培酮（RIS）是一种常用于治疗精神分裂症的常见药物。RIS 是一种疏水性药物，通常通过口服或肌肉注射给药。透皮给药（TDD）有可能改善 RIS 的递送。本研究首次专注于开发 RIS 纳米晶体（NCs），并将其纳入溶解微针贴片（DMAPs）中，以促进 RIS 的药物递送。RIS NCs 通过湿介质研磨技术，使用聚乙烯醇（PVA）作为稳定剂进行配方。制备出粒径为 300nm 的 NCs，显示出增强的释放特性，在 28 天内可达到 80%以上的释放。离体结果表明，与散装 RIS DMAPs 相比，从载有 NCs 的 DMAPs 向接收室和全厚皮肤输送的 RIS 为 1.16±0.04mg，而从散装 RIS DMAPs 输送的 RIS 为 0.75±0.07mg。在一项使用雌性 Sprague Dawley 大鼠进行的体内研究中，RIS 及其活性代谢物 9-羟基利培酮（9-OH-RIS）在血浆样品中均检测到 5 天。与口服组相比，DMAPs 改善了血浆中的整体药代动力学特征，曲线下面积（AUC）值提高了约 15 倍。这项工作代表了通过微针递送来递抗精神病药物 RIS，也为 MAP 在经皮递送给水难溶性药物提供了充分的证据支持。
