Nimodipine Lipid Nanoparticles Preparation Process, The Physical And Chemical Properties And Rats In Vivo Pharmacokinetic Studies

To overcome the disadvantages such as lower drug entrapment efficiency (EE) and loading (DL) of lipid nanospheres prepared by conventional solvent diffusion method, a solvent diffusion method in drug saturated aqueous system was developed. By using nimodipine as a model drug, the nimodipine loaded monostearin (MS) solid lipid nanoparticles (SLN) and MS nanostructured lipid carriers (NLC) with different caprylic/capric triglycerides (CT) content were produced by this method. The SLN produced by conventional method and employing different production temperature showed only 24.40-30.21 wt% EE, and the highest EE and slower drug release of SLN were achieved when the production temperature was 0℃. 20 wt% CT incorporated into SLN could enhanced the EE from 30.21 wt% to 50.35 wt%. As the drug saturated waters were used as continuous phase in steady of water, the EE of SLN and NLC could increase form 30.21 wt% to 42.45 wt%, and 50.35 wt% to 62.32 wt%, respectively. Moreover, the drug release was delayed by the use of drug saturated waters as a continuous phase. From Differential scanning calorimetry (DSC) analysis, it was clear that the drug contents in the surface of lipid nanospheres were significantly reduced when the drug saturated waters were used as continuous phase, and the drug content in lipid matrix increased. By increasing the CT content in lipid nanospheres, the EE and drug release of NLC was enhanced, and the particle size was reduced. The increasing of charged amount of drug could led to the lower EE, and the highest DL of NLC was reached up to 4.22 wt% as 8 wt % drug related with total amount of drug and lipid matrix was charged in the preparation of NLC. A RP-HPLC method was established to determine the concentration of nimodipine in plasma. Nimodipine NLC were prepared by solvent dispersion method, and its pharmacokinetics parameters and bioavailability in SD rats were studied after administration. Results showed that comparing with Nimotop tablet, the T_max of nimodipine NLC was delayed by 2.3h, and the bioavailability of nimodipine NLC increased 2.26 folds. Nimodipine NLC obviously enhanced the bioavailability of nimodipine in rats after oral administration.