Construction And Intestinal Absorption Research On Cinnamon Oil Microemulsion System

A safe and moderate fuel load Cinnamon oil microemulsion system (oil in water)was built in this paper. Its physical and chemical parameters was determined and itsstability, release in vitro and intestinal absorption were investigated in thisresearch.The main contents and results were as follows:1. Construction of Cinnamon oil microemulsion system(COMS)The COMS were prepared with phase inversion emulsification method and aamount of water added was precisely controlled by the conductivity method. Thecentrifugation was to determine the initial microemulsions, while the centrifugalresults and the sizes of microemulsion areas in pseudo-ternary phase diagrams wereto judge the stability of the microemulsions preliminarily. The raw materials andprocess parameters of the construction of COMS were preliminarily screened. Thefinal formunation of COMS optimized was Tween80/EL-40/glycerol/dehydratedethanol/IPM/Cinnamon oil/water, where Tween80:EL-40=3:1,glycerol:dehydrated ethanol=1:1, Cinnamon oil: IPM=1:1, Km=4. The preparationtemperature was40℃, and content of water was64.29%. The COMS wasoil-in-water microemulsion, pale yellow, clear and transparent. The average particlediameter of COMS was14.6nm and pH、conductivity、refractive index、viscositywere5.03、228μs/cm、1.3829、46.5mpa·s respectively.The content of Cinnamicaldehyde was21.27mg/mL.2. Investigation of the stability of COMSThe HPLC method established by our laboratory was referenced to determinatethe content of Cinnamic aldehyde. The stability of COMS was investigated byheating-cooling cycle test、high speed centrifuge test and thermostatic acceleratedtest.The results showed that there was good linearity between peak area and theconcentrations of Cinnamic aldehyde in the range of20μg/mL～160μg/mL and thestandard curve equation was y=162.7x+169(R2=0.998). In the heating and coolingcycle test and high speed centrifuge test, there were also no phase separation. In the thermostatic acceleration test, there were a little changes in parameters, in addition tothe pH value and the reserved rate of Cinnamic aldehyde content in COMSmaintained over90%after six months, while there was just46.52%in cinnamon oilunder the same conditions. It suggested that the COMS constructed in this researchwas a stable microemulsion system and could effectively reduce the loss of Cinnamicaldehyde.3. Release of COMS in vitroThe positive stage diffusion dialysis method was selected to investigated the release ofCOMS in artificial gastric juice, pH6.8and pH7.4artificial intestinal fluid, then thesituations of release were fitted respectively. The results showed that Cinnamic aldehydewas destroyed in artificial gastric juice and the five equations selected were unable todescribe their release conditions. But the residence time of the COMS in the stomachgenerally is no more than1.5hours in practical applications from the experimental result, soit has no or little effect on the release of substances such as Cinnamic aldehyde. The releaseconditions were different in artificial intestinal fluid with different pH value, while releaseconditions of the COMS both accorded with Retger-peppas equation in pH6.8artificialintestinal fluid and pH7.4artificial intestinal fluid, and release equation were Q=8.6642t0.6118(R2=0.9980)、Q=3.9064t0.7904(R2=0.9719), respectively.4. Intestinal absorption of COMSThe everted gut sac method was selected to investigate the intestinal absorptioncondition of COSM in vitro, and the intestinal absorption situations were comparedbetween COSM and the Cinnamon oil conventional emulsion. The results were that:①The absorption velocity of Cinnamic aldehyde in the small intestine was jejunum> duodenum> ileum, and intestines absorption of jejunum was significantly greaterthan duodenum and ileum respectivity.②The accumulate uptake of Cinnamicaldehyde did not have a increasing trend continuously with time increasing, but thecumulative absorption percentages of COMS were always higher than the Cinnamonoil conventional emulsion in the same time under the experimental conditions.The method of unidirectional intestinal perfusion was selected to investigate theintestinal absorption condition of COSM in vivo. The effects of the flow rate of constant flow pump and formulations on intestinal absorption were investigated. Theresults showed that:①The larger the flow rate of constant flow pump setted(204μL/min、301μL/min), the stage uptake and accumulate uptake of Cinnamicaldehyde were greater;②There was a good linear relationship between theintestinal accumulate uptake of Cinnamic aldehyde and absorption time (R2>0.99)under the conditions of this reseaech;③Under the same conditions, the Cinnamicaldehyde stage uptake of COMS was generally higher than the Cinnamon oilconventional emulsion, while the cumulate uptake and cumulate absorptionpercentages of COMS were higher than the Cinnamon oil conventional emulsion. Itsuggested that the intestinal absorption of COMS was better than the Cinnamon oilconventional emulsion. The bioavailability of COMS might be better than theCinnamon oil conventional emulsion.