Preparation And Evaluation Of Nifedipine Microemulsion

Nifedipine is the first generation of calcium antagonists, the drug which preventionand control of hypertension and angina pectoris, is one of the world’s best-selling drugin the mid-1980. But nifedipine poorly soluble in water, low bioavailability and shorthalf-life, individual difference is big. Therefore, to a certain extent, restrict the use ofnifedipine.Microemulsion is a kind of transparent or translucent, low viscosity, isotropicand the thermodynamic stability of the oil-water mixed systems which wasspontaneously formed in the appropriate proportion by the water phase, oil phase andsurfactant. As a ideal difficult soluble drug carrier, it has the following advantages: lowtoxicity, high security, simple preparation; can increase soluble in water solubility ofdrugs, can improve the stability of the easy hydrolysis drugs. Nifedipine preparationinto microemulsion type, to a certain extent, increased the solubility of nifedipine, thusimprove its bioavailability. The article main research content is as follows:1.Established a method for determination of the content of nifedipine—Uvspectrophotometry. Through to absorption curve, the wavelength235nm for nifedipinedetection is determined. And the concentration from2.0to16.0μg.ml^-1has a good linearrelationship for absorbance value, the regression equation as A=0.0639+0.0132C, r=0.9996.Then through to determin the stability test, within-day precision test, day to dayprecision test,the repeatability test, recovery test. The experimental results show that itcan maintain stable within24h, within-day precision and day to day precision is good,reproducibility and recovery rate are accordance with the requirements of themethodology.2.Preliminary screening and optimization study the nifedipine microemulsionprescription.Select dimethyl simethicone、ethyl oleate、atoleine as oil phase, tween-80、tween-20、lecithin、emulsifier OP as surfactant, anhydrous ethanol、n-butyl alcohol、glycerin、1,2propylene glycol、glycol as cosurfactant, observe and study nifedipinesolubility in each components for preliminary screening the basic formulation:ethyloleate as oil phase, tween-80、emulsifier OP as surfactant, anhydrous ethanol、1,2propylene glycol as cosurfactant. Using the compatibility of medicines analysis ofdifferent surfactants and ethyl oleate, determine the emulsifier OP as surfactant. Pseudoternary phase diagram is used to determine the blank microemulsion prescriptioncomponent: emulsifier OP, anhydrous ethanol, ethyl oleate, distilled water. Based microemulsion pseudo ternary phase graph, investigation the influence of Km andtemperature on the formation of microemulsion, choose Km value is2, and theexperiment temperature is room temperature. Investigation the influence of watercontent on the microemulsion drug loadings,conductivity, viscosity to optimizemicroemulsion prescription. End up with nifedipine microemulsion of best quality（m）ratio:emulsifier OP:anhydrous ethanol:ethyl oleate: water=27:13.5:4.5:55.3. The quality evaluation of nifedipine microemulsion. According to the optimization ofthe prescription and preparation methods of microemulsion, then prepare the nifedipinemicroemulsion, and carries on the quality evaluation. The experimental results showthat the nifedipine microemulsion which was a light yellow, clear, transparent andgood mobility, use staining method to prove it is O/W microemulsion, use rotationalviscometer to measure the viscosity is29.8687mpa/s, using electrical conductivitymeter measured the conductivity is127.62μs.cm^-1.The shape of microemulsion afterdiluted by water was spherical under ZEISS LIBRA200TEM transmission electronmicroscopy, and are uniformly distributed.Using Nano ZS90Zetasizer laser particlesize analyzer measured microemulsion with an average diameter of22.89nm;dispersion index （PDI） is0.128, particle size is uniformly distributed.And it showedgood stability after high speed centrifuging and reserved sample trimester to observe,and also their content and diameter had no obvious change. Nifedipine is almostinsoluble in water, solubility in water is about11μg·ml^-1, after the preparation ofmicroemulsion, the experiment results show that the content of nifedipine inmicroemulsion was7.7778mg·ml^-1, the solubility is raised more than700times.To sum up, with this method, nifedipine microemulsion performance stability, highsolubility, and the preparation method is simple, is expected to improve itsbioavailability, and provides a theoretical reference to the research on medicine newdosage form of nifedipine.