Pires Patrícia C, Fernandes Mariana, Nina Francisca, Gama Francisco, Gomes Maria F, Rodrigues Lina E, Meirinho Sara, Silvestre Samuel, Alves Gilberto, Santos Adriana O
CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal.
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal.
Pharmaceutics. 2023 Jul 4;15(7):1878. doi: 10.3390/pharmaceutics15071878.
Formulating low-solubility or low-permeability drugs is a challenge, particularly with the low administration volumes required in intranasal drug delivery. Nanoemulsions (NE) can solve both issues, but their production and physical stability can be challenging, particularly when a high proportion of lipids is necessary. Hence, the aim of the present work was to develop a NE with good solubilization capacity for lipophilic drugs like simvastatin and able to promote the absorption of drugs with low permeability like fosphenytoin. Compositions with high proportion of two lipids were screened and characterized. Surprisingly, one of the compositions did not require high energy methods for high droplet size homogeneity. To better understand formulation factors important for this feature, several related compositions were evaluated, and their relative cytotoxicity was screened. Optimized compositions contained a high proportion of propylene glycol monocaprylate NF, formed very homogenous NE using a low-energy phase inversion method, solubilized simvastatin at high drug strength, and promoted a faster intranasal absorption of the hydrophilic prodrug fosphenytoin. Hence, a new highly homogeneous NE obtained by a simple low-energy method was successfully developed, which is a potential alternative for industrial application for the solubilization and protection of lipophilic actives, as well as (co-)administration of hydrophilic molecules.
配制低溶解度或低渗透性药物是一项挑战，尤其是在鼻内给药所需的给药体积较小的情况下。纳米乳剂（NE）可以解决这两个问题，但其生产和物理稳定性可能具有挑战性，特别是在需要高比例脂质的情况下。因此，本研究的目的是开发一种对辛伐他汀等亲脂性药物具有良好增溶能力且能够促进磷苯妥英等低渗透性药物吸收的纳米乳剂。对含有高比例两种脂质的组合物进行了筛选和表征。令人惊讶的是，其中一种组合物不需要高能量方法就能实现高液滴尺寸均匀性。为了更好地理解对该特性重要的制剂因素，对几种相关组合物进行了评估，并筛选了它们的相对细胞毒性。优化后的组合物含有高比例的单辛酸丙二醇酯NF，使用低能相转变法形成了非常均匀的纳米乳剂，在高药物浓度下增溶了辛伐他汀，并促进了亲水性前药磷苯妥英的更快鼻内吸收。因此，成功开发了一种通过简单低能方法获得的新型高度均匀的纳米乳剂，它是一种在工业应用中用于增溶和保护亲脂性活性成分以及（共）给药亲水性分子的潜在替代品。
