| Object iceArtemisinin is extracted from Artemisia annua plants of compositae(Artemisia annua 1.)leaf,which is sesquiterpenoids containing oxygen groups.It has antimalarial activity,but single dose is easy to produce drug resistance and its derivatives are widely used to clinical medicine.Thus,the aim of this study was to prepare a high drug-loading Artemisinin/Lumefantrine compound of intravenous sub-micronized emulsion.Methods and resultsThe high performance liquid chromatography and thin layer chromatography was used for Qualitative and quantitative analysis methods of lumefantrine and artemisinin in Artemisinin/Lumefantrine compound of intravenous sub-micronized emulsion,the analysis method can effectively control the quality of the preparation.Artemisinin and lumefantrine may produced eutectic material using differential scanning calorimetry analysis(DSC)and IR analysis,besides,it showed that eutectic material largely increased solubility of artemisinin in oil phase by high performance liquid chromatography analysis.Respectively by single factor and orthogonal experiment,inspected the prescription and the preparation technology,the final formulation preparing process were as follows:glycerol,Pluronic F68,Tween80,sodium oleate were dissolved in water to obtain a water phase.Meanwhile,artemisinin,lumefantrine,SPC,MCT were co-dissolved to obtain an oil phase.The oil phase was added to the water phase and mixed using a mechanical agitation(500rpm,60?)to prepare the primary emulsion.Then the primary emulsion was passed through a high pressure homogenizer(500bar,10cycles).Finally,the product was gassed with N2 and sealed in glass bottles followed by sterilizing in a water bath at 100? for 30min.Investigation physical and chemical properties of Artemisinin/Lumefantrine compound of intravenous sub-micronized emulsion:preparation appearance:bright yellow emulsion,average particle size were 157 nm,pH 6-7.5,the drug loading capacity and the encapsulation efficiencyof artemisinin were 94.1%and 92.5%,while lumefantrine were 92.1%,and 90.7%,related substances examination in accordance with prescribed requirements.The particle size increased and the emulsions hung on wall after Psychro-thermal cycles above 3 times.Vibration wave stability experiments showed that combination Artemisinin intravenous lipid emulsion can withstand preparation,sterilization and transporting and storaging collision effects.Influencing factors of the test results show that Artemisinin/Lumefantrine compound of intravenous sub-micronized emulsion is unstable under thecondition of high temperature,light and high humidity.The preparations begin to change the physical and chemical properties after 2 months' Accelerated experiment at 25 ?,60%.Its physical and chemical properties change little in Long-term test within three months a t 4 ?,6 0%.Preliminary safety inspection showed that there were no vascular irritation,no hemolytic,and pyrogen inspection were in accordance with Chinese pharmacopoeia.LC-MS/MS technology is presented in this paper determining of artemisininand lumefantrine in rabbit body.The pharmacokinetic experiment of Artemisinin/Lumefantrine compound of intravenous sub-micronized emulsion found that artemisinin fits one room model,while lumefantrine fits two room model.Metabolism of artemisinin is faster,and the elimination time is shorter,comparing with lumefantrine.So two drugs were complemetary based on the pharmacokinetics.So as to achieve efficiency reduction,reducing the role of drug resistance.ConclusionArtemisinin and Lumefantrine formed the compound which increases the solubility of artemisinin in oil phase.The technology of preparing the Artemisinin/Lumefantrine compound of intravenous sub-micronized emulsion is feasible and the various physical and chemical properties,emulsion stability preparation.Besides animal experiments showed that artemisinin and lumefantrine are complementary in the pharmacokinetic,further demonstrates the feasibility of the prescription. |
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