Study On Phase Behaviors Of Hot Drug-Loading Microemulsion And Its Application

In this paper, phase behavior of a special microemulsion was studied, based on which the controllable preparation of nano drug carrier was realized.From the beginning of 1990's, Solid Lipid Nanoparticles (SLN) have been attached great importance. In most cases, the preparation of SLN lies on the property of microemulsion. So the study on the phase behavior of hot drug-loaded microemulsions is significative for the controllable preparation of SLN. In this paper, the microemulsion is quite different from normal microemulsion for the melt lipid as oil phase, so the temperature should remain between 60-80 ℃. Phase diagram of normal microemulsion is drawn through titration method, but it's not much suitable for the special microemulsion.The major achievements in this paper include: making of a microemulsion phase diagram detection instrument; studying on the phase behavior of different emulsifiers systems; succeeding in preparing SLN based on the phase behaviors results. As follows are the details:1. Making a microemulsion phase diagram detection instrument with high temperature accuracyIt consists of thermostatic unit, stirrer unit, sample cell, detector unit, and switch unit. Advantages are: 1) it can control temperature accurately and easily; 2) the use of stirrer makes it easier to observe phase variety; 3) the dark box is helpful to estimate the liquid crystal region .2. Studying on the phase behaviors of S-40/ F-68/glycerol monostearate (GMS)Water systemThe phase diagrams for the system S-40/F-68/water were obtained at 60°C with self-made device. The optimal mass ratio of S-40 and F-68 was chosen as 7:3 according to the phase behaviors results and experiment phenomena. With GMS added, the pseudoternary phase diagrams for the system S-40/F-68/GMS/water were obtained. It was concluded that the temperature and the introduction of retinoic acid (RA) has little influence on the phase behaviors of hot drug-loaded microemulsions. RA-SLN has been gotten when RA was chosen as model drug. It can also be obtain by freeze-drying. The mean particle size was measured by Photon Correlation Spectroscopy (PCS) method and the morphology of RA-SLN was characterized by Transmission Electron Microscope (TEM). The results show that the mean diameter of RA-SLN is between the 10-20nm. RA-SLN of various drug loading was prepared and the maximum can reach 327μg/mL. As far as stability of RA-SLN is concerned, it remains stable after 120 min centrifugation (4℃,10000 r/min) or 1 year storage for nano drug carrier. The transdermal permeation through rabbit skin in vitro indicated that RA-SLN is of better skin penetrating capacity.3. Studying on the phase behaviors of Brij78/ deoxycholic acid sodium(DAS)/GMS/Water system The pseudoternary phase diagrams of Brij78/DAS/GMS/water systems with different ratio of GMS were obtained at 60 ℃, the ratio separately was 10%, 20%, 33%, 50%. Only when the lipid content was comparatively low, O/W microemulsion region appeared in phase diagram. The ratio of 20% was considered optimal after comparing. It was concluded that the introduction of RA has some influence on the phase behaviors, especially for O/W microemulsion region and its region appeared to expand. Research of RA-SLN showed that: The mean particle size kept between 10-20nm. RA-SLN of various drug loading was prepared and the maximum can reach 327μg/mL. Besides, it has a good stability. Eyedrop loading with RA-SLN can inhibit metaplasia and proliferation of lens epithelial cells in rabbit eyes and prevent the development of posterior capsular opacification.