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薄荷醇和丙二醇对双载药溶致液晶凝胶经皮传递系统的评价。

The Evaluations of Menthol and Propylene Glycol on the Transdermal Delivery System of Dual Drug-Loaded Lyotropic Liquid Crystalline Gels.

机构信息

School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China.

Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei, 230012, China.

出版信息

AAPS PharmSciTech. 2020 Aug 4;21(6):224. doi: 10.1208/s12249-020-01762-5.

Abstract

This study aimed to evaluate the effects of two different structural alcohol permeation enhancers (menthol and propylene glycol) on the internal structure and in vitro properties of the dual drug-loaded lyotropic liquid crystalline (LLC) gels. The LLC gels were prepared and characterized by polarized light microscopy, small-angle X-ray scattering, differential scanning calorimetry, attenuated total reflectance-Fourier transform infrared spectrum, and rheology. Based on the results, the inner structure of the gels was Q mesophase and exhibited a pseudoplastic fluid behavior. The level of internal order in the LLC mesophase would be affected by introduced 2 wt% menthol (MEN) and propylene glycol (PG). The in vitro release experiment showed that the release behavior of sinomenine hydrochloride (SH) and cinnamaldehyde (CA) from the LLC system was dominated by Fickian diffusion (n < 0.43). MEN and PG had the opposite effects on the release of hydrophilic SH, while the MEN and PG both increased the release of lipophilic drug CA. Furthermore, in vitro permeation studies indicated that MEN and PG could both improve the skin permeability of SH and CA, and MEN displayed more pronounced enhancement. All the samples showed no skin irritation on the normal rat skin. Collectively, in our research, monoterpenoid MEN exhibited a better penetration-promoting effect than straight-chain fatty alcohol PG on the dual drug-loaded LLC system.

摘要

本研究旨在评估两种不同结构的醇类透皮促进剂(薄荷醇和丙二醇)对双载药溶致液晶(LLC)凝胶的内部结构和体外性质的影响。采用偏光显微镜、小角 X 射线散射、差示扫描量热法、衰减全反射傅里叶变换红外光谱和流变学对 LLC 凝胶进行了制备和表征。基于实验结果,凝胶的内部结构为 Q 相,并表现出假塑性流体行为。引入 2wt%薄荷醇(MEN)和丙二醇(PG)会影响 LLC 中间相的内部有序程度。体外释放实验表明,盐酸青藤碱(SH)和肉桂醛(CA)从 LLC 体系中的释放行为受菲克扩散控制(n<0.43)。MEN 和 PG 对亲水性 SH 的释放具有相反的影响,而 MEN 和 PG 均增加了疏水性药物 CA 的释放。此外,体外渗透研究表明,MEN 和 PG 均可提高 SH 和 CA 的皮肤渗透性,且 MEN 表现出更显著的增强作用。所有样品在正常大鼠皮肤上均无皮肤刺激性。综上所述,在本研究中,单萜类薄荷醇在双载药 LLC 体系中表现出比直链脂肪醇 PG 更好的促透作用。

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