| Metformin hydrochloride?MH?is a biguanide hypoglycemic agent.Clinically,it is a first-line drug for the treatment of type 2 diabetes.MH is a highly soluble,low-permeability BCS class III drug,in which intestinal permeability is a major factor affecting the oral absorption rate and process of MH.The purpose of this study is to improve the oral bioavailability of MH,improve the pharmacokinetic properties in vivo,in order to further improve the efficacy and reduce gastrointestinal side effects.Metformin hydrochloride and resveratrol compound nanoemulsion?MRCN?was prepared and used for oral delivery to achieve efficient sustained release of MH,improved absorption in the intestine,and improved bioavailability.In first part,the method for determining the in vitro content of MH in MRCN was established.High performance liquid chromatography?HPLC?was used to determine the MH content.The specificity,linearity,detection limit and limit of quantitation,precision,recovery and stability of the HPLC method were investigated.The experimental results are consistent with the requirements of the content determination method,which can be used for the determination of the content of MH in MRCN in vitro.In second part,MRCN was successfully prepared,and its appearance,particle size,zeta potential,encapsulation efficiency,pH,conductivity,optical rotation properties were investigated.The results showed that the appearance of MRCN was gray-yellow clarified emulsion,and the shape was spherical under transmission electron microscope?TEM?.The particle size is?17.29±0.29?nm,the zeta potential is?-0.494±0.024?mV,the encapsulation efficiency is?83.11±1.45?%,the pH value is 5.43±0.03,the conductivity value is?186.40±5.63??s/cm,and the specific rotation value ofis 194.74±4.44.In third part,a method for determining the content of MH in rat plasma samples was established,and the pharmacokinetic behavior of MRCN in rats was evaluated.The HPLC method established by the experiment is in accordance with the methodological requirements and can be used for the determination of MH in rat plasma.Compared with MH,the relative bioavailability of MRCN increased by 1.24 times,MRT?0-96 h?increased by 3.62 times,Tmax increased by 2.38 times,t1/2/2 increased by 4.25times,Cmax reduced by 54.77%,and Cl reduced by 18.04%.At the same time,AUC?0-96h?,Cmax,Tmax are not meet the bioequivalence standard,and MRCN is not equivalent to MH.In fourth part,the determination method of MH content in rat intestinal fluid was established,and the absorption kinetics of MRCN in different intestinal segments?duodenum,jejunum,ileum,colon?in rats was investigated.The results of the HPLC method established by the experiment are in accordance with the methodological requirements and can be used for the determination of MH content in rat intestinal fluid.Compared with MH,MRCN's absorption rate and extent in the duodenum,jejunum,ileum and colon were significantly improved.Absorption rate constant?Ka?,effective permeability coefficient(Peff)and percentage of absorption?PA?of MRCN were significantly higher than MH in all four intestinal segments. |
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