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目的:评价头孢丙烯国产口服制剂质量并初步预测生物等效性。方法:采用HPLC法分析原料及制剂的杂质谱变化,采用光纤探头与流通池法结合,模拟胃肠环境下,研究头孢丙烯片、分散片和胶囊的溶出曲线及溶出行为差异。HPLC法:采用Alltima-C_(18)色谱柱(4.6 mm×250 mm,3.5μm),柱温25℃,流速1.0 mL·min~(-1);有关物质测定时以0.23%磷酸二氢铵溶液—甲醇的为流动相,梯度洗脱,检测波长为225 nm;溶出曲线实验时,以磷酸二氢铵溶液(称取磷酸二氢铵20.7 g.加水1 800 mL使溶解,用磷酸调节pH至4.4)-乙腈(90∶10)为流动相,检测波长为280 nm。光纤溶出法:分别以水、介质1、介质2为溶出介质,溶出体积900 m ,采用转篮法,转速为100 r·min~(-1),分别在4、8、10、30 min时取样。流通池法:以水、介质1、介质2为溶出介质,温度37.0℃,流速4 mL·min~(-1),分别在3、6、10、15、30 min时取样。结果:国产头孢丙烯制剂中主要杂质为头孢羟氨苄,属工艺杂质;各剂型中头孢羟氨苄与总杂质控制较好,分别约含0.3%和0.4%左右;与专利药相比,无明显差异;国产头孢丙烯片具有与专利药相同的体外溶出行为;分散片和胶囊的体外溶出行为与片剂相似,无明显差异,表现为快速释放。结论:头孢丙烯国产口服制剂质量较好,工艺较稳定;国产头孢丙烯片与专利药相比,药品质量无差异,体外溶出实验初步预测二者生物等效;而分散片和胶囊的快速溶出,对保证头孢丙烯的临床抗菌效果是有利因素。
OBJECTIVE: To evaluate the quality of domestic oral formulations of cefprozil and to preliminary predict the bioequivalence. Methods: The changes of impurity spectra of raw materials and preparations were analyzed by HPLC. The dissolution curves and dissolution behaviors of cefprozil tablets, dispersible tablets and capsules were studied by using optical fiber probe combined with flow cell method to simulate gastrointestinal environment. The HPLC method was as follows: Alltima-C_ (18) column (4.6 mm × 250 mm, 3.5 μm) was used. The column temperature was 25 ℃ and the flow rate was 1.0 mL · min -1. Solution-methanol as the mobile phase, gradient elution, detection wavelength of 225 nm; dissolution curve experiment, with ammonium dihydrogen phosphate solution (weighed 20.7 g of ammonium dihydrogen phosphate solution to dissolve with 1 800 mL with phosphoric acid to adjust the pH To 4.4) - acetonitrile (90:10) as the mobile phase, the detection wavelength was 280 nm. Optical fiber dissolution method: Take water, medium 1 and medium 2 as the dissolution medium respectively, and the dissolution volume is 900 m. The rotating speed is 100 r · min ~ (-1) at the spinning speed of 100 r · min ~ sampling. Flow cell method: water, medium 1, medium 2 as the dissolution medium, temperature 37.0 ℃, flow rate 4 mL · min ~ (-1), respectively, at 3,6,10,15,30 min samples. Results: The main impurity in domestic cefprozil preparation was cefadroxil, which was a process impurity. Cefadroxil and total impurities in each dosage form were controlled well, with about 0.3% and 0.4% respectively. Compared with the proprietary drugs, there was no significant difference ; Domestic cefprozil tablets have the same in vitro dissolution behavior as the patented drugs; the dissolution behavior of the dispersible tablets and capsules in vitro is similar to that of the tablets, with no significant difference, showing rapid release. Conclusion: The quality of domestic oral formulations of cefprozil is better and the process is more stable. Compared with the proprietary drugs, domestic cefprozil tablets showed no difference in drug quality, and bioequivalence was initially estimated in vitro dissolution experiments. The rapid dissolution of dispersible tablets and capsules, It is a favorable factor to ensure the clinical antibacterial effect of cefprozil.