缓释异烟肼生物蛋白胶的制备及体外释放特征研究

Preparation of fibrin sealant with sustained-release isoniazid and in vitro release characteristic

目的为探讨采用生物蛋白胶携带异烟肼的方法制备异烟肼缓释制剂新剂型的可行性,对该剂型的制备及体外缓释特点等进行研究。方法将50 mg异烟肼融入配制好的生物蛋白胶中,制取异烟肼-生物蛋白胶凝胶薄片。将薄片浸入生理盐水,分别在12 h、24 h、36 h、48 h、60 h、72 h、84 h、96 h、108 h以及120 h时采用高效液相色谱法对其体外释放率进行检测,根据所得标准曲线计算累计释放率,色谱条件为流动相甲醇-磷酸氢二钠(75∶25,pH=4.5,0.02 mol/L),检测波长为254 nm,流速为1 ml/min,柱温为30℃。结果该异烟肼-生物蛋白胶凝胶薄片易于制备且性状稳定;高效液相色谱异性较高,保留时间约为3.8 min,未检测到其他物质对生物胶内异烟肼测定的干扰;高效液相色谱重复性好,结果可靠,RSD=0.92%;吸收峰面积(A)及浓度线性关系良好,线性方程为A=3.449C-0.381,回归系数r=0.887;该制剂缓释效果好,在前24 h内缓释生物蛋白胶异烟肼释放最为明显,该趋势可持续到72 h以上;84 h后蛋白胶薄片开始显著溶解,但到120 h时仍未完全溶解。结论生物蛋白胶携带异烟肼制备简单易行,体外缓释效果良好。

Objective To explore the preparation of fibrin sealant with sustained-release isoniazid and study in vitro re- lease characteristics. Methods 50 mg isoniazid was dissolved in prepared fibrin glue to prepare isoniazid-fibrin glue slice. The slice was immersed into physiological saline. High performance liquid chromatography（HPLC） was applied at 12 h,24 h,36 h,48 h,60 h,72 h,84 h,96 h,108 h and 120 h to detect in vitro release rate,and the cumulative release rate was calculated based on acquired standard curve. The HPLC system was consisted of methanol-disodium hydrogen phosphate （75 ： 25, pH = 0.45,0.02 tool/L）, detecting wave length 254 nm, flow rate 1 ml/min, column temperature 30 ℃. Results The isoniazid-fibrin glue shce was stable and easy to be prepared;HPLC showed high specificity of detection, based on the evidence that the persistence time was 3.8 min and no other substances were detected ; the repeatability of the detection was reliable because of the RSD = 0.92%. There was a linear relationship between peak area （A） and concentration （ C ） ： A = 3. 449C - 0.381, r = 0. 887 ; The sustained release effect was well, obvious in the first 24 h, sustaining till 72h;slice began to dissolve from 84 h,but didn＇t dissolve completely until 120 h. Conclusion The fibrin glue carrying isoniazid is easy to be prepared and there is a confirmed sustained release effect of in vitro.