ABSTRACT
The aim of this paper was to investigate and compare the penetration-enhancing characteristics of menthol and essential oil from Mentha haplocalyx(M.haplocalyx oil) on the transdermal absorption of the complex traditional Chinese medicine(TCM) components. A series of TCM components were selected as model drugs based on their lipophilicity (logP value), namely osthole(OT, logP=3.85), tetramethylpyrazine(TMP, logP=2.34), ferulic acid(FA, logP=1.26), puerarin(PR, logP=-0.35) and geniposide(GP, logP=-1.01), in order to simply and characterize the TCM complex components system. Transdermal experiment in vitro was employed to investigate and compare the penetration-enhancing characteristics of menthol and M.haplocalyx oil on the transdermal absorption of these model drugs. Meanwhile, Fourier transform infrared spectroscopy(FTIR) was used to further compare the effect of menthol and M. haplocalyx oil on the molecular structure of stratum corneum(SC). The results showed that both of menthol and M.haplocalyx oil at proper concentration could promote the transdermal absorption of the selected model drugs. After application of menthol, the drug logP values gradually tended to have negative linear relationship with the logarithm of penetration enhancement ratio(ER); while after application of M.haplocalyx oil, the logP values tended to have parabolic relationship with the logarithm of ER. However, both menthol and M.haplocalyx oil exhibited higher efficiency for the drugs with relative low lgP value(ie hydrophilic drugs), with similar penetration-enhancing characteristics between these two. Infrared spectroscopy results showed that menthol and M.haplocalyx oil could affect the skin barrier functions mainly via stratum corneum lipids, with similar effect intensity, and this was consistent with the results of transdermal experiment in vitro. Thus, Menthol had similar penetration-enhancing characteristics with M.haplocalyx oil, and had same effect on the SC molecular structure. Therefore, as transdermal penetration enhancer, the menthol with single composition could be considered to replace M.haplocalyx oil with complex compositions.
ABSTRACT
To optimize the matrix formulation of Chaizhi cataplasma (CC) and investigate its release and transdermal absorption properties in vitro. The optimized matrix formulation of cataplasma containing liquid herbal extract is determined by using D-optimal mixture design, with initial bonding strength, endurance bonding strength and gel strength as the evaluating indicators. Modified Franz diffusion cells were used to study the in vitro release and transdermal absorption of geniposide in CC. The optimized matrix formulation of CC contained NP700, aluminum glycinate, tartaric acid, glycerin, PVPK90 and water (9∶0.7∶0.8∶30∶5∶30.5). Cumulative release rate of geniposide in CC was (77.02±3.73)% in 24 h. The percutaneous penetration rate of geniposide was 7.25 μg•cm⁻²•h⁻¹ and the 24 h permeated amount was (156.22±4.90) μg•cm⁻². The optimized CC prepared by the D-optimal mixture design showed a good adhesion and formability. The in vitro release of the geniposide in CC was in accordance with the first order equation, while its in vitro transdermal absorption was close to the zero order equation.
ABSTRACT
To prepare pellets of supercritical fluid extraction (SFE) of Angelica Sinensis Radix by using the ionic crosslinking method, and the drug loading and encapsulation efficiency were used as the index to investigate the multiple factors which may impact the drug loading and encapsulation efficiency. Box-Behnken design and response surface analysis method were then taken to optimize the prescription of pellets and study the coating technology. Through the study on the release of pellets in vitro, an optimal coating technology and prescription of colon-specific pellets of Angelica Sinensis Radix SFE were selected and their colon targeting was evaluated. The optimal preparation parameters of pellets were determined as follows： 3% pectin; 4∶1 for pectin/lecithin; 4∶5 for pectin/SFE of Angelica Sinensis Radix; 4% zinc acetate solution as crosslinking agent, blending temperature 35 ℃, crosslinking temperature 35 ℃, crosslinking time 30 min; coating technology： coating material Eudragit FS 30D, 1.5% triethyl citrate and polyoxyethylene sorbitan monooleate（tween-80）, 1.2% monostearin and 15% coating weight gained. The colon-specific pellets of Angelica Sinensis Radix SFE prepared with optimized conditions were almost not released in simulated gastric fluid in 2 h, released less than 20% in simulated intestine fluid in 4 h, and released more than 90% in simulated colon fluid in 6 h, indicating that the colon-specific pellets of Angelica Sinensis Radix SFE had an excellent colon targeting property.
ABSTRACT
The aim of this paper was to investigate the effect of terpene penetration enhancers on membrane fluidity and membrane potential using HaCaT keratinocytes, and study the potential mechanisms of these terpene compounds using as natural transdermal penetration enhancer. Six terpene compounds, namely menthol, limonene, 1,8-cineole, menthone, terpinen-4-ol and pulegone, were chosen in this study on account of their good penetration-enhancement activities. The cytotoxicity of these terpene compounds was measured using an MTT assay. The fluorescence recovery after photobleaching (FRAP) technique was employed to measure the change of membrane fluidity of HaCaT cells. The flow cytometer was used to study the alteration of membrane fluidity of HaCaT cells, and investigate the effect of terpene compounds on intracellular Ca2+. It was found that 6 terpene compounds possessed low cytotoxicity in comparison to the well-established and standard penetration enhancer azone. Those terpene compounds could significantly enhance HaCaT cells membrane fluidity and decrease HaCaT cells membrane potentials. Meanwhile, after treated with various terpene compounds, the Ca2(+)-ATPase activity and intracellular Ca2+ of HaCaT cells was decreased significantly. Terpene penetration enhancers perhaps changed the membrane fluidity and potentials of HaCaT cells by altering the Ca2+ balance of the cell inside and outside, resulting in the low skin permeability to increase the drug transdermal absorption.