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用于盐酸拉贝洛尔透皮给药的水凝胶形成微阵列贴片与粉末型储库相结合。

Hydrogel-forming microarray patches combined with powder-based reservoir for labetalol hydrochloride transdermal delivery.

作者信息

Anjani Qonita Kurnia, Detamornrat Usanee, Larrañeta Eneko, Donnelly Ryan F

机构信息

School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.

School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.

出版信息

Int J Pharm. 2025 Jan 25;669:125061. doi: 10.1016/j.ijpharm.2024.125061. Epub 2024 Dec 7.

Abstract

Hypertension is the most common pregnancy disorder and can lead to life-threatening conditions for both mother and fetus. However, managing this condition with oral and intravenous labetalol can be challenging, highlighting the need for alternative delivery methods. This study presents, for the first time, the development of novel powder-based reservoirs incorporated with hydrogel-forming microarray patches (MAPs) to facilitate the transdermal delivery of labetalol hydrochloride (HCl). A holder, created from poly(propylene) using a 3D printer, was designed to house labetalol HCl powder, which was then combined with hydrogel-forming MAPs. This novel system improved the insertion profile of MAPs into Parafilm® layers and excised full-thickness neonatal porcine skin, achieving up to 85 % of needle height penetration without compromising needle integrity (only 8 % height reduction after applying 32 N of force). The current holder design was able to load 50 mg of labetalol HCl and allowed for single or multiple injections of deionised water to dissolve the powder and facilitate permeation through dermatomed neonatal porcine skin in in vitro studies using a Franz cell setup. The results showed that this powder-based reservoir design delivered labetalol HCl more effectively over 24 h compared to directly compressed tablets. Additionally, poly(vinyl alcohol)/poly(vinyl pyrrolidone)/citric acid-based hydrogel-forming MAPs delivered more labetalol HCl than Gantrez® S-97/poly(ethylene glycol)-based MAPs (9 mg vs. 5 mg) in 24 h. This novel system holds promise for improving the delivery of compounds in a simple manner, though further design modifications for one-step application are needed.

摘要

高血压是最常见的妊娠疾病,可导致母亲和胎儿面临危及生命的状况。然而,使用口服和静脉注射拉贝洛尔来控制这种疾病可能具有挑战性,这凸显了对替代给药方法的需求。本研究首次展示了新型粉末型储库与形成水凝胶的微阵列贴片(MAPs)相结合,以促进盐酸拉贝洛尔的透皮给药。使用3D打印机由聚丙烯制成的支架被设计用于容纳盐酸拉贝洛尔粉末,然后将其与形成水凝胶的MAPs相结合。这种新型系统改善了MAPs插入Parafilm®层和切除的新生猪全层皮肤的情况,在不损害针头完整性的情况下实现了高达85%的针高穿透率(施加32 N力后针头高度仅降低8%)。当前的支架设计能够装载50 mg盐酸拉贝洛尔,并允许单次或多次注射去离子水以溶解粉末,并在体外研究中使用Franz扩散池装置促进其透过新生猪皮的渗透。结果表明,与直接压制片剂相比,这种基于粉末的储库设计在24小时内更有效地递送了盐酸拉贝洛尔。此外,基于聚乙烯醇/聚乙烯吡咯烷酮/柠檬酸的形成水凝胶的MAPs在24小时内递送的盐酸拉贝洛尔比基于Gantrez® S - 97/聚乙二醇的MAPs更多(分别为9 mg和5 mg)。尽管需要对一步应用进行进一步的设计修改,但这种新型系统有望以简单的方式改善化合物的递送。

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