利培酮-环糊精包合物储库联合水凝胶形成型微针贴片增强经皮给药。
Risperidone-cyclodextrin complex reservoir combined with hydrogel-forming microneedle array patches for enhanced transdermal delivery.
机构信息
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.
出版信息
Eur J Pharm Biopharm. 2024 Sep;202:114415. doi: 10.1016/j.ejpb.2024.114415. Epub 2024 Jul 14.
Hydrogel-forming microneedle array patches (HFMAPs) are microneedles that create microconduits upon insertion and swelling in the skin, potentially allowing prolonged drug delivery without generating sharps waste. Delivering hydrophobic drugs using HFMAPs poses challenges, which can be addressed using solubility enhancers such as cyclodextrins (CDs). This study aimed to deliver risperidone (RIS) transdermally using HFMAPs. To enhance the aqueous solubility of RIS hydroxypropyl-beta-cyclodextrin (HP-β-CD) and hydroxypropyl-gamma-cyclodextrin (HP-γ-CD) were utilised and their performance was tested using phase solubility studies. The aqueous solubility of RIS was enhanced by 4.75-fold and 2-fold using HP-β-CD and HP-γ-CD, respectively. RIS-HP-β-CD complex (CX) and physical mixture (PM) directly compressed tablets were prepared and combined with HFMAPs. Among the tested formulations, RIS-HP-β-CD PM reservoirs with 11 x 11 PVA/PVP HFMAPs exhibited the best performance in ex vivo studies and were further evaluated in in vivo experiments using female Sprague Dawley rats. The extended wear time of the MAPs resulted in the sustained release of RIS and its active metabolite 9-hydroxyrisperidone (9-OH-RIS) in plasma samples, lasting from 3 to 5 days with a 1-day application and up to 10 days with a 5-day application. For a 1-day application, HFMAPs showed greater systemic exposure to RIS compared to intramuscular control (AUC: 13330.05 ± 2759.95 ng/mL/hour versus 2706 ± 1472 ng/mL/hour). Moreover, RIS exposure was extended to 5 days (AUC: 12292.37 ± 1801.94 ng/mL/hour). In conclusion, HFMAPs could serve as an alternative for delivering RIS in a sustained manner, potentially improving the treatment of schizophrenia.
水凝胶形成的微针贴片(HFMAPs)是在插入和在皮肤中膨胀时形成微通道的微针,有可能在不产生尖锐废物的情况下延长药物输送。使用 HFMAPs 输送疏水性药物存在挑战,可以使用增溶剂如环糊精(CDs)来解决。本研究旨在使用 HFMAPs 经皮输送利培酮(RIS)。为了提高 RIS 的水溶解度,使用了羟丙基-β-环糊精(HP-β-CD)和羟丙基-γ-环糊精(HP-γ-CD),并通过相溶解度研究测试了它们的性能。RIS 的水溶解度分别提高了 4.75 倍和 2 倍。直接压片制备了 RIS-HP-β-CD 配合物(CX)和物理混合物(PM),并与 HFMAPs 结合。在所测试的制剂中,RIS-HP-β-CD PM 储库与 11×11 PVA/PVP HFMAPs 联合使用,在离体研究中表现出最佳性能,并在雌性 Sprague Dawley 大鼠的体内实验中进一步进行了评估。MAPs 的延长佩戴时间导致 RIS 及其活性代谢物 9-羟基利培酮(9-OH-RIS)在血浆样品中的持续释放,持续时间为 3 至 5 天,单次应用持续 1 天,5 天应用持续 10 天。单次应用时,HFMAPs 显示出比肌肉内对照更高的 RIS 全身暴露量(AUC:13330.05±2759.95ng/mL/hour 与 2706±1472ng/mL/hour)。此外,RIS 暴露时间延长至 5 天(AUC:12292.37±1801.94ng/mL/hour)。总之,HFMAPs 可以作为一种替代方法,以持续的方式输送 RIS,有可能改善精神分裂症的治疗效果。