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

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 II 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.