Study On The Cubic Liquid Crystal Precursor Injection Of Sinomenine Hydrochloride

Objective:To prepare an in situ cubic liquid crystal precursor containing sinomenine hydrochloride?SH?for articular injection with the function of drug sustained-release by formula optimization,establish methods to characterize its internal structure,evaluate its in vitro release property and pharmacokinetics characteristics.Methods:An in situ cubic liquid crystal precursor of SH was prepared based on a three-componentssystemofglycerolmonoolein?GMO?-cosolvent-water.The appearance,injectability,pH value,gelation time and water for gelation of the obtained preparation were used as reference indicators to choose the best prescription.The physical properties and internal structures of the cubic liquid crystals were investigated and analyzed.The phase conversion of the liquid crystal precursors before and after the water-absorption was observed using polarized light microscopy.The Small angle X-ray scattering was further used to determine the internal arrangement of GMO molecules.The Rheology experiments were then performed on the water-absorbing liquid crystals to reveal the rheological properties of the formulations.The content of SH was determined by the high performance liquid chromatography,and the in vitro release behavior of liquid crystals was determined by dynamic dialysis using a self-made SH solution as a control group.In addition,the male SD rats were used as the model animals to establish a microdialysis technique to dynamically sample blood and joint cavity of rats and to detect the pharmacokinetics of the selected formulations.Results:The optimal formulas selected was:monoolein?55wt%?,ethanol:propylene glycol?10:15??25wt%?,sinomenine hydrochloride?10.60mg/g?,and sodium hyaluronate?0.75 mg/kg?,water?20wt%?.The optimal formulation was transparent liquid without phase separation,easily injected with a suitable pH,Polarized light microscopy and small-angle X-ray scattering results showed a cubic phase after transmistion on excess water.Rheological experiment results showed the water-absorbed gel was a non-Newtonian liquid with pseudoplasticity;In vitro release studies have shown that the drug can be sustained for more than one week.The pharmacokinetics experimental results showed that the in situ cubic liquid crystal can effectively prolong the retention time of SH in the joint cavity and reduce the drug's entry into the blood circulation.The plasma concentration results of rats showed that the AUC_?0-??and C_maxax of SH in the aqueous solution group were significantly higher than those of the cubic liquid crystal precursor group,while the MRT_t-?and t_maxax of the cubic liquid crystal precursor group were both greater than those of the aqueous solution group;Concentration in rat joint cavity test showed that the t_1/2,t max,and MRT_?0-??of the cubic liquid crystal group were significantly increased compared with the aqueous solution group.Conclusion:The SH cubic liquid crystal precursor injection selected in this experiment has a simple preparation process,controllable quality,and a good sustained-release effect.