Yalcin Tahir Emre, Anjani Qonita Kurnia, Li Yaocun, Larrañeta Eneko, Paredes Alejandro J, Donnelly Ryan F
Department of Pharmaceutical Technology, Faculty of Pharmacy, Gazi University 06330 Ankara, Türkiye; 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.
Int J Pharm. 2025 Oct 15;683:126019. doi: 10.1016/j.ijpharm.2025.126019. Epub 2025 Jul 30.
Parkinson's disease is a progressive neurodegenerative disorder, with rasagiline mesylate (RM), a potent MAO-B inhibitor, used to manage symptoms. However, oral RM administration often leads to gastrointestinal side effects, reducing patient compliance. This study explores dissolving microneedles (DMNs) and hydrogel-forming microneedles (HMNs) for transdermal RM delivery. DMNs exhibited uniform drug distribution, while HMNs showed even polymer dispersion and sharp needle tips. The formulated DMNs and HMNs demonstrated less than 15 % height reduction against 32 N pressure for 30 s, and insertion studies using an artificial Parafilm® M indicated sufficient needle mechanical properties to reach the dermal microcirculation. The selected DMNs drug content was 1.41 ± 0.11 mg with ∼ 70 % of RM retained in the baseplate due to drug migration during manufacturing. In situ dissolution studies showed that, this formulation fully dissolved within 60 min when applied to full-thickness neonatal porcine skin. Stability assessments confirmed that the active compound remained stable with no significant degradation after 4 weeks of storage for DMNs and reservoirs. In vitro permeation studies demonstrated that optimum DMNs formulation delivered approximately 928.2 ± 198.8 μg of the active compound over 24 h, corresponding to about 65 % of its content. HMNs delivered 6.44 mg and 18.32 mg of RM at 6 h and 24 h, corresponding to ∼ 20 % and ∼ 60 % delivery, respectively. These findings highlight the potential of microneedles as a viable transdermal RM delivery system, offering an alternative to oral administration, while maintaining controlled drug release and stability.
帕金森病是一种进行性神经退行性疾病,甲磺酸雷沙吉兰(RM)作为一种有效的单胺氧化酶B(MAO-B)抑制剂,用于控制症状。然而,口服RM常常会导致胃肠道副作用,降低患者的依从性。本研究探索了用于经皮递送RM的溶蚀性微针(DMN)和水凝胶形成微针(HMN)。DMN表现出药物分布均匀,而HMN显示出聚合物分散均匀且针尖尖锐。所制备的DMN和HMN在32 N压力下保持30 s后,高度降低小于15%,并且使用人工Parafilm® M进行的插入研究表明,针具有足够的机械性能以到达真皮微循环。所选DMN的药物含量为1.41±0.11 mg,由于制造过程中的药物迁移,约70%的RM保留在基板中。原位溶解研究表明,该制剂应用于新生仔猪全层皮肤后60分钟内完全溶解。稳定性评估证实,活性化合物保持稳定,DMN和储库在储存4周后没有明显降解。体外渗透研究表明,最佳的DMN制剂在24小时内递送约928.2±198.8 μg的活性化合物,相当于其含量的约65%。HMN在6小时和24小时时分别递送6.44 mg和18.32 mg的RM,分别相当于约20%和约60%的递送量。这些发现突出了微针作为一种可行的经皮RM递送系统的潜力,为口服给药提供了一种替代方案,同时保持了药物的控释和稳定性。