| The ever-increasing demands on the performance of pharmaceutical formations with respect to,e.g.,storage stability, decreased dosage level, higher bioavailability, fewer side effects, controlled release,and biological response(such as tissue distribution)constitute the main motivation for drug delivery research.Surfactants play a key role in many of the novel drug delivery systems developed,and a wide range of surfactant-containing systems.including parenteral emulsions, liposomes,liquid crystalline phase, cyclodextrins and microemulsions,are being extensively investigated in relation to drug delivery.Microemulsions are fluid, transparent, thermodynamically stable oil and water systems,stabilized by a surfactant usually in conjunction with a cosurfactant,which may be a short chain alcohol,amine or other weakly amphiphilic molecule. Microemulsions are novel carriers for many drugs. The pharmaceutical use of microemulsions as drug delivery systems around the world is no more than one decade until recently.We chose the system contained of non-ironic surfactant emulsifier OP/ isopropanol/isopropyl myristate/water, according to the phase diagram,as the basic prescription to prepare the oil-in-water microemulsion. Physicochemical properties (conductance, refractive index, viscosity and mean droplet diameter) of a serial of microemulsions contained of differentratio of OP and isopropanol(Km) and different ratio of oil and water were measured.The tendency of change and influence factors of these physicochemical properties were investigated, too.The result shows: refractive index and conductance of the blank microemulsion were influenced by the ratio of water/oil,and Km had predominately influence to the viscosity and mean droplet diameter of microemulsion. When Km increased,system viscosity would increase but the diameter would decrease.Famotidine is a histamine HZ receptor antagonist advocated for use in gastrointestinal ulcer and Zollinger-Ellison syndrome.In this study we prepared famotidine oral microemulsion solution.The formulations of prescription were finally optimized by the test of absorption using in situ perfusion method in rat jejunum. The morphology and particle size distribution of famotidine microemulsion was studied by electron microscopy and PCS method.HPLC method was chosen to determine the concentration of famotidine, which was convenient,rapid,accurate and suitable for assay of famotidine in the preparation.The average recovery was 97.63%,RSD was 0.72%(n=3).And temperature accelerated test suggested the famotidine oral microemulsion solution had been stable at 40℃ for 3 months.The HPLC method was adopted for the determination of famotidine in plasma. In rabbit,the standard curve was linear in the range of 10~500ng/ml(r:=0.9980),the limit was 5 ng/ml,the average recovery rate was 93.56?.73%,the within day and between day precision of determination of famotidine was 0.029 + 0.010,0.055 + 0.012, respectively.To study the pharmacokinetic progress of famotidine in rabbit,famotidine microemulsion and famotidine tablet were single-orally given to 8 animals.HPLC method determine the concentration of famotidine in plasma.AUC were calculated using the trapezoidal rule.Cmax and Tmax were obtained from the raw data.The AUC,Cmax and Tmax of microemulsion and tablet in this study were 957.77(ng/ml) ?h 900.89(ng/ml) -h; 1.31?.26h, 1.44?.32h; 243.61 ?150.30ng/ml 231.83 ?123.46ng/ml.The MRT was3.50h and 3.65h,respectively.The data weredisposed using the program 3P97 and the AUC of famotidine after the oral administration of microemulsion in the present study was significantly increased compared with the famotidine tablet.Therefore,we drew a conclusion that microemulsion system was a hopeful carrier for famotidine.. |
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