Queen's University, Belfast School of Pharmacy, 97 Lisburn Road, Belfast BT9 7BL, UK.
Queen's University, Belfast School of Pharmacy, 97 Lisburn Road, Belfast BT9 7BL, UK; School of Pharmacy, Zarqa University, Zarqa 132222, Jordan.
J Control Release. 2014 Apr 28;180(100):71-80. doi: 10.1016/j.jconrel.2014.02.007. Epub 2014 Feb 17.
We describe formulation and evaluation of novel dissolving polymeric microneedle (MN) arrays for the facilitated delivery of low molecular weight, high dose drugs. Ibuprofen sodium was used as the model here and was successfully formulated at approximately 50% w/w in the dry state using the copolymer poly(methylvinylether/maleic acid). These MNs were robust and effectively penetrated skin in vitro, dissolving rapidly to deliver the incorporated drug. The delivery of 1.5mg ibuprofen sodium, the theoretical mass of ibuprofen sodium contained within the dry MN alone, was vastly exceeded, indicating extensive delivery of the drug loaded into the baseplates. Indeed in in vitro transdermal delivery studies, approximately 33mg (90%) of the drug initially loaded into the arrays was delivered over 24h. Iontophoresis produced no meaningful increase in delivery. Biocompatibility studies and in vivo rat skin tolerance experiments raised no concerns. The blood plasma ibuprofen sodium concentrations achieved in rats (263μgml(-1) at the 24h time point) were approximately 20 times greater than the human therapeutic plasma level. By simplistic extrapolation of average weights from rats to humans, a MN patch design of no greater than 10cm(2) could cautiously be estimated to deliver therapeutically-relevant concentrations of ibuprofen sodium in humans. This work, therefore, represents a significant progression in exploitation of MN for successful transdermal delivery of a much wider range of drugs.
我们描述了新型溶解聚合物微针(MN)阵列的配方和评估,用于促进低分子量、高剂量药物的传递。在这里,我们使用布洛芬钠作为模型药物,并成功地以大约 50%w/w 的比例在干燥状态下使用共聚物聚(甲基乙烯基醚/马来酸)进行了配方设计。这些 MN 坚固耐用,能够有效地穿透皮肤,在体外迅速溶解以传递所包含的药物。输送 1.5mg 布洛芬钠,即干燥 MN 中所含布洛芬钠的理论质量,大大超过了这一水平,表明大量输送了载入基底片中的药物。实际上,在体外透皮给药研究中,最初载入阵列中的约 33mg(90%)药物在 24 小时内被输送。离子电渗法没有显著增加药物的输送。生物相容性研究和体内大鼠皮肤耐受实验没有引起任何担忧。在大鼠中达到的血浆布洛芬钠浓度(24 小时时为 263μgml(-1))大约是人类治疗性血浆水平的 20 倍。通过从大鼠到人类的平均体重的简单外推,设计面积不超过 10cm(2)的 MN 贴片可以谨慎估计在人类中以治疗相关浓度输送布洛芬钠。因此,这项工作代表了 MN 在成功透皮传递更广泛范围的药物方面的重大进展。