Studies On The Matrin Microemulsion

To screen out the prescription of O/W matrin microemulsion and study the effect of components and their proportion on the formation of microemulsion. Pseudo-ternary phase diagrams had been constructed for microemulsion systems comprising of water-surfactants -oil. Cremophor CO40,Cremophor EL-35 and monostearin were used as surfactant,several short chain alcohol (ethanol, 1,2-propylene glycol, n-butanol) were investigated as co-surfactants and IPM, GTCC, olive oil, wheat germ oil as oil. Based on the section size of microemulsion, stability and the content of matrin, screen out the appropriate prescription of matrin microemulsion. The results show the extent of the microemulsions' region is dependent on the natures of the surfactant and the oil, and also the surfactant/co-surfactant mixing ratio (Km).When the HLB value of mixtured surfactant is equal to the oil's, microemulsion can easily be made. Whether co-surfactants existed, Cremophor CO40 and Cremophor EL-35 can form microemulsion, but monostearin can't. The section of microemulsion containing co-surfactant is bigger, but its stability is worse. The system of microemulsion containing of IPM/Cremophor CO40/water is chosed to produce O/W microemulsions as drug delivery. The prime prescription of O/W matrin microemulsion is: matrin1.98 g, Cremorphor CO40 4.80 g, IPM 1.20 g, distilled water 10.00g.To study the quality and safety of matrin microemulsion. Observed the form of it under TEM. Measured its particle size and its distribution, using Zetasizer Nano ZS. Determined the content of matrin in the microemulsion and its stability. The cutaneous irritation experiment was carried out on the health rabbit. The results show matrin microemulsion is a kind of transparent liquid. We found that particle of microemulsion almost exist in the form of sphaeroid and distributes uniformly by the figure and particle diameter of microemulsion with the method of transmission electron microscope. Its average diameter is 70nm, but the blank microemultion without matrin is 65 nm. Physicalst stability and long-term stability of the system have also been studied. The results show that the stability of the matrin microemulsion is better. But it should be stored without strong light. The content of matrin in microemulsion was determined using spectrophotometric and determined at 415 nm. Microemulsion without matrin almost has no absorbtion at 415 nm. The standard curve is A=0.0466C+0.0876 (r=0.9997), the average recovery rate is 99.73%; the inter-day and intra-day precision of determination of matrin is less than 1%. And the content of matrin in microemulsion is 110.12mg/mL. Skin stimulative experiment's results show matrin microemulsion is safe.Study the percutaneous penetration of matrin microemulsion and the effect of different concertration of azone on it. With optimized franz diffuse well, male SD rat's skin and 0.9 % Nacl solution as the acceptor solution, comparision the permeability between matrin microemulsion and matrin solution was performanced. The results show the permeation rate of matrin microemulsion and matrin solution are 21.427μg/(cm2?h) and 16.332μg/(cm2?h) respectively. The accumulative penetration amount of matrin microemulsion and matrin solution are 230.23μg/cm2 and 197.23μg/cm2 respectively within 12h. And azone can increase the accumulative penetration amount of matrin miceoemultion. When the concentration of azone is 5%, the permeation rate and the cumulative penetration amount of matrin miceoemultion are 39.548μg/(cm2?h)and 428.17μg/cm2 respectively, and the time lag is shorter comparatively. So, 5% azone is best for the matrin microemulsion as the cutaneous permeation enhancer.MTT method was used to detect the matrin microemulsion against B16 melanoma cells in vitro under diferent drug concentration. The results show that matrin microemulsion has better activities on melanoma cells. When the concentration of matrin are 5 ~ 10μg/mL, there is no obvious difference between the matrin microemulsion and matrin solution (P>0.05), but the inhabiting rate of matrin microemulsion outgo the matrin solution's. When the concentration of matrin is 50 ~ 800μg/mL, there is obvious difference among the three groups (P<0.05), and the inhibition rate of matrin microemulsion obviously outgo the matrin solution's (P<0.05). And the morphology of cells in the matrin microemulsion have obviously changed. The cells become small and round. The amount of cells have obviously decreased. There are some cell fragments in the culture solution. Many cells have the structure of vacuole. The inhibition rate of blank microemulsion is 13.34%. According the evaluation standard of toxicity on cells, the grade of blank microemulsion is the first, so it is safe.Above all, the matrin microemulsion is stable, safe and effective, according to the standards of microemulsion and drug delivery.