Formulation and optimization of ivermectin nanocrystals for enhanced topical delivery

IF 5.2 2区 医学 Q1 PHARMACOLOGY & PHARMACY International Journal of Pharmaceutics: X Pub Date : 2023-09-07 DOI:10.1016/j.ijpx.2023.100210
Hoda Awad , Mutasem Rawas-Qalaji , Rania El Hosary , Jayalakshmi Jagal , Iman Saad Ahmed
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Abstract

The increasing resistance to antiparasitic drugs and limited availability of new agents highlight the need to improve the efficacy of existing treatments. Ivermectin (IVM) is commonly used for parasite treatment in humans and animals, however its efficacy is not optimal and the emergence of IVM-resistant parasites presents a challenge. In this context, the physico-chemical characteristics of IVM were modified by nanocrystallization to improve its equilibrium water-solubility and skin penetration, potentially improving its therapeutic effectiveness when applied topically. IVM-nanocrystals (IVM-NC) were prepared using microfluidization technique. The impact of several process/formulation variables on IVM-NC characteristics were studied using D-optimal statistical design. The optimized formulation was further lyophilized and evaluated using several in vitro and ex vivo tests. The optimal IVM-NC produced monodisperse particles with average diameter of 186 nm and polydispersity index of 0.4. In vitro results showed an impressive 730-fold increase in the equilibrium solubility and substantial 24-fold increase in dissolution rate. Ex vivo permeation study using pig's ear skin demonstrated 3-fold increase in dermal deposition of IVM-NC. Additionally, lyophilized IVM-NC was integrated into topical cream, and the resulting drug release profile was superior compared to that of the marketed product. Overall, IVM-NC presents a promising approach to improving the effectiveness of topically applied IVM in treating local parasitic infections.

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增强局部给药的伊维菌素纳米晶体的配方和优化
抗寄生虫药物耐药性的增加和新药物的有限供应凸显了提高现有治疗效果的必要性。伊维菌素(IVM)通常用于人类和动物的寄生虫治疗,但其疗效并不理想,抗IVM寄生虫的出现带来了挑战。在这种情况下,IVM的物理化学特性通过纳米化进行了修饰,以提高其平衡水溶性和皮肤渗透性,局部应用时可能会提高其治疗效果。采用微流控技术制备了IVM纳米晶体(IVM-NC)。采用D-最优统计设计研究了几个工艺/配方变量对IVM-NC特性的影响。将优化的制剂进一步冻干,并使用几项体外和离体测试进行评估。最佳的IVM-NC产生了平均直径为186nm、多分散指数为0.4的单分散颗粒。体外结果显示平衡溶解度显著增加730倍,溶解速率显著增加24倍。使用猪耳朵皮肤进行的离体渗透研究表明,IVM-NC的真皮沉积增加了3倍。此外,冻干IVM-NC被整合到局部乳膏中,与市场上的产品相比,所得到的药物释放特性更好。总之,IVM-NC为提高局部应用IVM治疗局部寄生虫感染的有效性提供了一种很有前途的方法。
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来源期刊
International Journal of Pharmaceutics: X
International Journal of Pharmaceutics: X Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.60
自引率
0.00%
发文量
32
审稿时长
24 days
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