中国药物经济学2016，Vol.11Issue(11)：11-16,6.DOI:10.12010/j.issn.1673-5846.2016.11.002
盐酸氨溴索注射剂稳定性及体内药物动力学的深层次评价
In-depth evaluation of stability and in vivo pharmacokinetics of Ambroxol Hydrochloride Injections
摘要
Abstract
Objective To deep evaluate stability and pharmacokinetics of four ambroxol hydrochloride injections at physiological pH.Methods pH 7.4 phosphate buffer solution (PBS) was used to simulate physiological pH of blood, and the content and pH change of four preparations were measured after mixed with pH7.4 PBS at different dosages. The plasma concentration of ambroxol hydrochloride was determined by HPLC-MS/MS,and pharmacokinetics of four ambroxol hydrochloride preparations in beagle dogs were investigated by randomized,self-crossed design.Results In pH 7.4 PBS,A and B two ambroxol hydrochloride water injection were relatively stable;for C and D two powder injection of ambroxol hydrochloride for injection, content decreased at low-dose, and decreased more than 10% at high-dose.The buffering ability of four preparations was obviously different,and buffering ability of water injection was obviously stronger than that of powder injection.The bioavailability of C and D preparations in medium and high doses was significantly lower than that of A preparation, suggesting that differences in formulation of ambroxol hydrochloride injection may affect bioavailability of drug.The biological half-life t1/2 of four preparations changed with increasing dose, and AUC(0-∞) showed a nonlinear increased trend with increasing dose,indicating that pharmaco- kinetics of drug may be nonlinear pharmacokinetic processes.Conclusion The stability of ambroxol hydrochloride in PBS was enhanced by addition of buffer system in formulation of ambroxol hydrochloride injection,which was beneficial to improve in vivo stability of drug.关键词
盐酸氨溴索/缓冲能力/HPLC-MS/MS/生物利用度/质量评价Key words
Buffer capacity/HPLC-MS/MS/Bioavailability/Quality evaluation分类
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张秀磊,钱江辉,任筱青,沙先谊..盐酸氨溴索注射剂稳定性及体内药物动力学的深层次评价[J].中国药物经济学,2016,11(11):11-16,6.
