| More and more facts showed that developing new drug could not support the therapy progress yet during recent years, the appropriate drug carrier system could overcome the problems existed at present and also satisfy the special requirement of control release and drug target delivery. At the beginning of 1990s, solid lipid nanoparticle (SLN) system was introduced as a novel carrier system, and was regarded as combined advantages of polymer nanoparticle and the O/W fat emulsion, simultaneity avoided the obviously disadvantages of the two systems. Therefore SLN was turned into one of the hotspots in the field of pharmacy.For the property of the materials,the parameter of the preparation and the structure characteristics of the drug and lipid in the SLN should all play crucial roles on the vivo performance of drug carrier, from the point of view of materials investigation,the pharmaceutical method was united in present work. Without adding organic solvent,modified high shear and ultrasound method was employed to produce the drug loaded SLN system with considerate physical stability, preferably entrapment efficiency (EE%) and favorable release properties. The modified method used in experiments was combined melt homogenization method with high shear and ultrasound techniques to produce SLN colloidal system, and two times high shears and ultrasounds should be performed in water bath with the temperature not less than 10℃ above the lipid melt point.The sample prepared with high shear method delaminated soon, and superstratum was turbid with the lager mean particle size than clarifying underlayer. The two suspension systems were lied average particle in lager size range and with big polydispersity index at all. The one produced by the ultrasound method with long time presented two model distribution of particle, and there was no micro particle observed, but the metal Ti pollution should be taken into account for the long time probe ultrasound. The mean particle size of sample prepared with once high shear and ultrasound was larger than that of modified method, the system was performed several model distribution with the semitransparent nanosuspension of mean particle size of 165nm, and lager particles in micron range was detected. The nano system prepared by modified method presented single model of very narrow particle distribution, with mean particle size of 102nm, and the system performed excellent physical stability. Model drug mifepristone was an effective abortifacient. Combined several surfactants the sample was produced with average particle size of about 100nm, and also showed favorable long term storing stability. It was regarded that regular crystal lattice was substituted with defects, for the crystallization of SLN samples was decreased sharply than that of the matrix from XRD and DSC investigations. As a result it could supply place to accommodate foreign drug. Certain amount of materials could only accommodate certain amount of foreign drug molecular, and extra drug adding could not improve the EE%. With the increase of drug adding, average particle size and Zeta potential of system were improved for the amount of free drug increased, and the physical state of free drug was also altered from crystalline state to amorphism resulting from DSC measurements. The EE% of the lyophilization sample added 20% trehalose was as high as 73% with mean particle size of 247nm (versus 109nm before lyophilization). The vitro release property of nano systems did not show remarkable difference, but micron system performed rapid release at the beginning compared the nanosuspensions, with almost complete release (about 91%) at the first 24hr. therefore, the nano carrier systems could prolong the release of drug encapsulated in them.In the structure of triptolide SLN prepared with mixed materials, two matrixes were still existed in two states: liquid oil and solid lipid, for the respective melting property of low and normal temperature DSC investigations and different molecular mobile state of NMR measurements. The... |
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