Preparation And Quality Evaluation Of Emodin Oral Mixed Micelles

Emodin,from the polygonaceae plants separated radix et rhizoma rhei,Rhizoma Polygoni Cuspidati,etc,is the main effective monomer,and a kind of orange long needle crystal,melting point is 256?²57?.It is almost insoluble in water and soluble in ethanol and alkali solution.Emodin has antibacterial,diuretic,anti-inflam-matory,cholagogic,antitussive,antihypertensive,effect on promoting gastrointestinal peristalsis,dilating blood vessels and so on.In recent years,emodin is clinically used to treat pancreatic cancer,breast cancer and lung cancer.Therefore,emodin,as an antitumor drug or as an adjuvant to inhibit tumor cell growth drug,has a very wide application prospect.However,emodin hydrophilicity and lipotropy are less,leading to its low solubility in water and do'not favor the injected.Its pharmacokinetic differences in rabbit body,oral drug absorption rate and absorption degree is very low,will enter the body after the body appear sudden release phenomenon,and limit its clinical application.It was found that two or more surfactants could significantly increase the solubility and dissolution rate of the indissolvable drugs in aqueous solution after forming the mixed micelle system.Therefore,in order to solve the emodin undissolved in water and the problem of low dissolution,theresearchwould preparethe emodin oral mixed micelles with some mixed carrier materials.The emodin oral mixed micelles would improve the solubility and the dissolution rateof emodin,increase the degree of absorption,and boost its bioavailability.Theresearch chose tween 80 and poloxamer 407 two carrier material to prepare the oral mixed micelle emodin.The physical and chemical propertiesof the oral emodinmixed micelle has been characterized in vivo and in vitro,and the distribution of the organizationin mice has been studied.1.A high performance liquid chromatography?HPLC?for determination of emodin was established.Results show that the 5.0⁷0 mu g/mL,within the scope of concentration,concentration of emodin and good linear relationship between peak area?A=48.004-168.51 c,R²=0.9999?,days and daytime precision<2%,the recovery rate was between 96.43%⁹9.53%,emodin solution is stable within 20 h.At the same time,the apparent oil and water distribution coefficient of emodin was determined by this method,the logP_app of emodin in various pH PBS were between 0 and 0.4.2.The oral mixing micelle of emodin was prepared by direct dissolution method,and the combination of various materials was investigated.When tween 80 and poloxam407 were used together,a transparent and stable micelle could be formed.The interaction between tween 80,poloxamer 407 and emodin was studied by fluorescence spectrometry and Uv-vis spectrophotometry.The results showed that tween 80 and poloxamer 407quenched the fluorescence of tween 80 and poloxamer 407 by forming matrix complexes with emodin.3.Preparation technology and prescription optimization of emodin oral mixed micelle.Through single factor experiment investigation to drug loadings,the envelopment rate as an index,the micelle drug loadings and the envelopment rate have obvious influence factors include:polysorbate 80 mooring los gresham?mg?,407?mg?,and o-phenylenediamine?mg?and hydration volume?mL?.Further experiments with center combination-response surface method optimization to get the optimal prescription for:the amount of tween 80 to 300 mg,amount of 3.93 mg lpoloxame 407,emodin content is 0.72mg,hydration volume of 3.69 mL,according to the author of micelle the envelopment rate and the fuel load were 96.92%,0.23%respectively.4.Characterization of physical and chemical properties of emodin oral mixed micelle.The results showed that the average particle size of the micelle was 7.264 nm,the PDI value was 0.468,and the Zeta potential was-7.12mV.Under transmission electron microscope,the micelle is spherical and the size is not sticky.The CMC of the mixed micelle is 1.26 mg/mL.The results of DSC,TGA,XRD and IR showed that the crystalline structure of emodin in the micelle disappeared,indicating that it was contained in the micelle core.The in vitro release experiment of artificial gastric juice and artificial intestinal juice showed that emodin-propanediol group reached drug release balance at 6 h,while micelle group reached drug release balance at 12 h.The sudden release of the latter decreased significantly and the slow-release effect increased.5.Study on the pharmacokinetics of emodin oral mixed micelle.The pharmacokinetics of emodin orally mixed micelle and emodin suspension in Wistar rats were investigated.The results showed that the elimination process of emodin was in accordance with the two-compartment model,and the blood concentration of emodin was high and reached the peak rapidly,and its half-life was 6.5 times longer than that of emodin suspension solution.The results showed that the plasma retention time of emodin in the form of mixed micelles was longer,which could improve the bioavailability of drugs and the therapeutic effect of drugs.6.Study on tissue distribution of emodin mixed micelle in mice.The results show that the micellar concentration in the liver peaked at 8 h,and distribution in the liver than emodin mixed suspension increased 2.4 times,show that micellar easily distributed in liver and spleen,and the distribution of emodin in the heart,lung,kidney volume difference is small,the amount is low,can reduce the heart,lung and kidney toxicity.7.Ultrafiltration-HPLC was used to study the binding rate of emodin with plasma protein of rats and bovine serum albumin.The results showed that the binding rates of emodin with plasma protein of rats and bovine serum albumin were 94.0%and 85.3%,respectively.The binding constant K of emodin and bovine serum albumin was 5.51×10⁴L/mol,and the binding site n was 0.05.It can be seen from molecular simulation that the action of emodin and BSA is mainly hydrophobic and hydrogen bonding,and the interaction between ions exists.