Souza de Araujo Guilherme Rodolfo, Mendonça da Cruz Macieira Givalda, Xavier de Oliveira Dayane, Santos Matos Saulo, Nery Dos Santos Quesia, Otubo Larissa, Antunes de Souza Araújo Adriano, Cavalcante Duarte Marcelo, Moreira Lira Ana Amélia, de Souza Nunes Rogéria, Vitorino Sarmento Victor Hugo
Department of Pharmacy, Federal University of Sergipe, Av. Marechal Rondon, Jd. Rosa Elze, São Cristóvão, s/n 49100-000 SE, Brazil.
Department of Chemistry, Federal University of Sergipe, Av. Vereador Olimpio Grande, Sítio Porto, Itabaiana, s/n 49506-036 SE, Brazil.
Colloids Surf B Biointerfaces. 2022 Jun;214:112474. doi: 10.1016/j.colsurfb.2022.112474. Epub 2022 Mar 23.
Nifedipine is a potent anti-hypertensive, which is poorly orally bioavailable on account of first-pass metabolism, short half-life, and low water solubility. This study aimed to develop a microemulsified system with low surfactant concentration and to evaluate the influence of microemulsion (ME) phase behavior on skin permeation of nifedipine, as drug model. Thereafter, MEs were obtained using PPG-5-CETETH-20, oleic acid, and phosphate buffer at pH 5.0. The selected MEs were isotropic, with droplet diameters less than 10 nm, polydispersity index < 0.25, and pH between 5.0 and 5.2. MEs presented low viscosity and Newtonian behavior. SAXS results confirmed bicontinuous and oil-in-water (o/w) MEs formation. The presence of the drug promoted only very slight modifications in the ME structure. The MEs presented ability to deliver nifedipine via the transdermal route when in comparison with the control. Nevertheless, the skin permeated and retained amounts from the o/w and bicontinuous formulations did not differ significantly. The ATR-FTIR demonstrated that both formulations promoted fluidization and disorganization of lipids and increased the drug diffusion and partition coefficients in the skin. In conclusion, PPG-5-CETETH-20 MEs obtained proved to be effective skin permeation enhancers, acting by rising the coefficients of partition and diffusion of the nifedipine in the skin.
硝苯地平是一种强效抗高血压药物，由于首过代谢、半衰期短和水溶性低，其口服生物利用度较差。本研究旨在开发一种表面活性剂浓度低的微乳体系，并评估微乳（ME）相行为对作为药物模型的硝苯地平经皮渗透的影响。此后，使用PPG - 5 - CETETH - 20、油酸和pH为5.0的磷酸盐缓冲液获得微乳。所选微乳为各向同性，液滴直径小于10 nm，多分散指数<0.25，pH在5.0至5.2之间。微乳呈现低粘度和牛顿流体行为。小角X射线散射结果证实了双连续和水包油（o/w）微乳的形成。药物的存在仅对微乳结构产生非常轻微的改变。与对照相比，微乳具有通过透皮途径递送硝苯地平的能力。然而，来自o/w和双连续制剂的皮肤渗透量和滞留量没有显著差异。衰减全反射傅里叶变换红外光谱（ATR - FTIR）表明，两种制剂均促进了脂质的流化和无序化，并增加了药物在皮肤中的扩散系数和分配系数。总之，所获得的PPG - 5 - CETETH - 20微乳被证明是有效的皮肤渗透促进剂，其作用是提高硝苯地平在皮肤中的分配系数和扩散系数。
