Ring Spore, A Solid Lipid Nanoparticle Preparation Process Optimization And Performance Study

Solid lipid nanoparticles(SLN) had many obvious advantages such as showing good sustained-release characteristics and being appropriate for administering through multiple channels, so it had become a focus recently. Taking tristearin as the main carrier material, the classical immunosuppressants cyclosporine A as the drug model and solvent diffusion method as the preparation technology, the cyclosporine A-loaded solid lipid nanoparticles were prepared. Due to the formation of calcium alginate gel by adding Ca2+into solution containing sodium alginate, cyclosporine A-loaded SLN could be separated at low speed of centrifugation and the entrapment efficiency could be determined easily and exactly. In this paper, optimal conditions of higher entrapment efficiency were gained by response surface design. The properties of SLN were studied, such as surface morphology, the average size and the Zeta electric potential. The stability and the drug release behavior in vitro were systematically researched. This paper offered some theory and experimental information for SLN applied in clinical.The main conclusions are as follows:1. Though Plackeet-Burman experiment, water and temperature were the two obvious factors in the eight elements of affecting the entrapment efficiency. The centre point was identified as0.11g sodium alginate,60ml water and35℃temperature by the steepest ascent experiment. The optimal technical condition was0.1132g sodium alginate,52.77ml water and34.55℃temperature determined by the center of Box-Behnken design experiment. Under the optimal technical condition, the actual drug encapsulation efficiency was82.45%, close to the predictive value of83.98%.2. With the optimal condition, cyclosporine A-loaded SLN was prepared with rod-like shape and satisfied monodisperse. The average size was181.3nm and the Zeta electric potential was-57.0mV.3. Factor experiment proved that cyclosporine A-loaded SLN dispersions belong to thermodynamically unstable systems and high temperature and light had a certain effect on the storage of SLN dispersions.4. In vitro release experiments confirmed that the cyclosporin A-loaded SLN had a sustained-release characteristics. The release process consisted of two stages:burst release and sustained release. In different medium, the release rate of cyclosporine A-loaded SLN was simulated intestinal fluid> artificial gastric fluid>0.1%SDS solution. In the there media, the release mechanism of cyclosporin A-loaded SLN was Fikc diffusion-based, supplemented by the skeleton dissolution.