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目的:评价在国家结核病控制规划中大范围供应使用抗结核药物固定剂量复合剂(FDC)的质量,尤其是FDC中利福平的溶解特性。方法:对4家药厂供应的4种制剂采用不同的溶媒(0.1NHCL及0.01NHCL、磷酸缓冲液(PB)及含20%植物油的PB)、不同振荡强度(USPⅡ型仪)进行溶解度研究。并对FDC进行了4周的催化稳定性研究(40℃/75%相对湿度[RH]),评价其物理、化学和溶解稳定性。结果:根据药典中的质控试验(CQC)对待评价制剂进行检测。利福平的溶解程度不受溶媒影响;有两种产品的利福平溶解速度有轻微降低。75%以上的药物成分在除30rpm外的各种振荡强度下,代表饱食状态的含20%植物油溶媒中45分钟内溶解。在制药厂建议的包装条件下,各制剂至少在4周内性能稳定。结论:所检测的制剂均通过了质量控制试验并证明其性能稳定。虽然有的制剂溶解速度有所降低,但其溶解程度未发生改变,但这就需要胃及肠道不同PH条件下的多点溶解,以保证制剂体内生物利用度的稳定性。
PURPOSE: To evaluate the quality of the broad-based supply of anti-TB drug fixed-dose combination (FDC) in national TB control programs, especially the dissolution profile of rifampicin in FDC. Methods: The solubility of four preparations supplied by four pharmaceutical factories were measured with different solvents (0.1N HCL, 0.01N HCl, PB and 20% vegetable oil) and different shaking intensities (USP II). The FDC was also studied for its catalytic stability (40 ° C / 75% relative humidity [RH]) for 4 weeks to evaluate its physical, chemical and dissolution stability. Results: The formulations to be evaluated were tested according to the quality control test (CQC) in the Pharmacopoeia. The solubility of rifampin is unaffected by the vehicle; there are two products with a slight decrease in the rate of rifampicin dissolution. More than 75% of the drug ingredients dissolve within 45 minutes in 20% vegetable oil vehicle in a saturated state at various shake intensities except 30 rpm. The formulations are stable for at least 4 weeks at the pharmaceutical manufacturer’s recommended packaging conditions. Conclusion: The tested formulations passed the quality control test and proved their performance is stable. Although the rate of dissolution of some preparations decreased, the degree of dissolution did not change, but this required multi-point dissolution under different pH conditions in the stomach and intestine to ensure the stability of the bioavailability of the preparation in vivo.