Study On The Construction Of Lipid-based Cubic Liquid Crystalline Of FT And The Bioavailability Of Re-construction After Solidification And Liquidation

OBJECTIVEThis thesis mainly studies about Lipid-based Cubic Liquid Crystalline micropatricle,taken FT as the model medicine. This study was generally prepared with the followingprocedures. First, by adopting the High Temperature Input Method, the lipid-based cubiccrystal particles of FT are prepared, and then dried into powdered form with the SprayDrying Technology. After the preparation procedure, characterization of the lipid-basedcubic crystal particles is conducted with micropolariscope and transmission electronmicroscope. The studies of the release rate of FT in vitro and pharmacokinetics of oraldoses in rats were conducted at last.METHODS AND RESULTS1、Preparation of lipid-based cubic crystal particles of FT.Due to that FT is less water soluble, the High Temperature Input Method is adoptedto prepare lipid-based cubic crystal particles of this medicine. This experiment led to anoptimal emulsifier after sieve——F127. Then characterization can be conducted withmicropolariscope and transmission electron microscope. As known, when excessive, FTwould form crystalline so as to present birefringent properties under micropolariscope, while presenting gloomy the other way around. By knowing this characteristic, we candraw ternary phase diagram to determine the maximal drug-loading rate of FT inlipid-based cubic crystals, witch is6.5%when water-oil rato is3:7.2、Determination of the entrapment efficiency of FT lipid-based cubic crystal particles.Then these particles are solidified into powdered form with the Spray DryingTechnology and Freeze-Drying Technology. By drying the lipid-based cubic crystalparticles, platform of drug loading and solidification of lipid-based cubic liquid crystallinemicropatricle is constructed. At the same time, a comparison of the two technologies ofdrying and solidifying is also made.3、Study of the release rate of FT in vitro.By comparing the dissolution of lipid-based cubic crystal of FT and Pharmaceuticalraw materials of FT-at11hours, the accumulated release of them equils to99.53%and44.36%, it can be proved that lipid-based cubic crystal particles can evidently improve therelease rate of less dissolvable medicines like FT in vitro. Then the determination methodof corresponding HPLC has been constructed.4、Study of pharmacokinetics of oral doses in rats.This study would adopt SD rats as experiment animals. With intragastricadministration of re-liquidation prepared lipid-based cubic crystal of FT to rats, bloodsamples are collected from the rats’ fossa orbitalis in a certain period of time. Thesesamples would then be determined by HPLC after pre-treatment. In the end, thecorresponding pharmacokinetics parameters can be calculated and derived with3P97software. The Tmax of lipid-based cubic crystal particles and suspension of FT equals to4.6750h and5.1700h; The t1/2(ka) equals to1.9600and2.4186h; The t1/2(α) equals to3.4464h and2.9975h, The Cmax equals to88.6018μg ml-1and6.5973μg ml-1, The AUCequals to1435.7289μg h ml-1and131.6853μg h ml-1. This indicates that lipid-basedcubic crystal particles can sifnificantly improve the absorbing of FT by bioligicalmembrane, which thus increases the bioavailability of FT.