Objective This study aimed to design and optimize the water extraction process for Chuantieling(喘贴灵,CTL)based on the concept of quality by design(QbD).Methods The single-factor experiments were used to select the b...Objective This study aimed to design and optimize the water extraction process for Chuantieling(喘贴灵,CTL)based on the concept of quality by design(QbD).Methods The single-factor experiments were used to select the best experimental points of CTL water extraction.On this basis,the transfer rate of ephedrine hydrochloride and sin-apine thiocyanate,and the yield of the extract were evaluated as the evaluation indicators.The liquid-solid ratio,extraction time,and pH value were selected as the main factors to carry out the Box-Behnken design(BBD).A mathematical model of the critical process parameters(CPPs)and critical quality attributes(CQAs)was established,the interaction between CQAs and CPPs was examined,and the CTL extraction process design space was established and optimized,which guaranteed the stability of the process.The high performance liquid chro-matography(HPLC)was used to analyze the main active compounds in the CTL extract.Results Through single-factor experiments,the best experimental parameters were found to be a liquid-solid ratio of 8∶1,extraction time of 90 min,pH value of 4,and extraction times of three.The experimental variance analysis results of the BBD showed that the P value of the re-gression model was less than 0.05,and the lack-of-fit value was greater than 0.01,indicating that the constructed model had good predictive ability.The operating space of the CPPs of the CTL water extraction process was combined with the actual production situation.In the pro-duction situation,the best extraction process was nine times of water addition,72 min of ex-traction time,and 4.5 of pH value.The HPLC results showed that the peak areas of ephedrine hydrochloride,sinapine thiocyanate,tetrahydropalmatine,methyl eugenol,cinnamaldehyde,and 6-gingerol in the CTL extract accounted for 0.94%,14.32%,0.78%,31.23%,0.34%,and 0.44%of the total peak area,respectively.Conclusion The water extraction process design space of CTL based on QbD was conducive to actual production operations,ensuring the stability of the process.展开更多
目的:建立益心泰颗粒的HPLC指纹图谱,为其质量评价提供依据。方法:采用Phenomenext Luna C_(18)色谱柱(250 mm×4.6 mm,5μm),以0.1%磷酸溶液-甲醇为流动相,检测波长为286 nm,体积流量为1.0 m L·min^(-1);柱温为30℃。测定10...目的:建立益心泰颗粒的HPLC指纹图谱,为其质量评价提供依据。方法:采用Phenomenext Luna C_(18)色谱柱(250 mm×4.6 mm,5μm),以0.1%磷酸溶液-甲醇为流动相,检测波长为286 nm,体积流量为1.0 m L·min^(-1);柱温为30℃。测定10批益心泰颗粒样品,应用中药色谱指纹图谱相似度评价系统(2012版)建立益心泰颗粒指纹图谱共有模式图,并计算相似度,再通过对照品色谱图对共有峰进行指认。结果:通过10批样品的测定,建立益心泰颗粒HPLC指纹图谱,计算得相似度为0.98。共标定31个共有色谱峰,其中4个共有峰19、25、30、31号峰为黄芪药材的专属峰;7个共有峰3、20、21、22、23、24、28号峰为丹参的专属峰;9个共有峰6、7、11、12、13、14、26、27、29号峰为红花的专属峰;6个共有峰8、10、15-18号峰为葶苈子的专属峰;1个共有峰5号峰为泽泻专属峰;1、9号峰为红花、泽泻的共有峰,2号峰为红花、茯苓的共有峰,4号峰为猪苓、丹参的共有峰。并通过对照品色谱图对共有峰进行指认,12、19、21、25、30号峰分别为羟基红花黄色素A、毛蕊异黄酮苷、丹酚酸B、芒柄花素、毛蕊异黄酮。结论:10批样品相似度结果表明该颗粒制备工艺方法稳定可行,同时建立的HPLC指纹图谱方法稳定可靠。展开更多
基金Hunan University of Traditional Chinese Medicine Graduate Training Quality Engineering Project(2019CX57)the First-class Discipline Project on Chinese Pharmacology of Hunan University of Chinese Medicine (201803)。
文摘Objective This study aimed to design and optimize the water extraction process for Chuantieling(喘贴灵,CTL)based on the concept of quality by design(QbD).Methods The single-factor experiments were used to select the best experimental points of CTL water extraction.On this basis,the transfer rate of ephedrine hydrochloride and sin-apine thiocyanate,and the yield of the extract were evaluated as the evaluation indicators.The liquid-solid ratio,extraction time,and pH value were selected as the main factors to carry out the Box-Behnken design(BBD).A mathematical model of the critical process parameters(CPPs)and critical quality attributes(CQAs)was established,the interaction between CQAs and CPPs was examined,and the CTL extraction process design space was established and optimized,which guaranteed the stability of the process.The high performance liquid chro-matography(HPLC)was used to analyze the main active compounds in the CTL extract.Results Through single-factor experiments,the best experimental parameters were found to be a liquid-solid ratio of 8∶1,extraction time of 90 min,pH value of 4,and extraction times of three.The experimental variance analysis results of the BBD showed that the P value of the re-gression model was less than 0.05,and the lack-of-fit value was greater than 0.01,indicating that the constructed model had good predictive ability.The operating space of the CPPs of the CTL water extraction process was combined with the actual production situation.In the pro-duction situation,the best extraction process was nine times of water addition,72 min of ex-traction time,and 4.5 of pH value.The HPLC results showed that the peak areas of ephedrine hydrochloride,sinapine thiocyanate,tetrahydropalmatine,methyl eugenol,cinnamaldehyde,and 6-gingerol in the CTL extract accounted for 0.94%,14.32%,0.78%,31.23%,0.34%,and 0.44%of the total peak area,respectively.Conclusion The water extraction process design space of CTL based on QbD was conducive to actual production operations,ensuring the stability of the process.
文摘目的:建立益心泰颗粒的HPLC指纹图谱,为其质量评价提供依据。方法:采用Phenomenext Luna C_(18)色谱柱(250 mm×4.6 mm,5μm),以0.1%磷酸溶液-甲醇为流动相,检测波长为286 nm,体积流量为1.0 m L·min^(-1);柱温为30℃。测定10批益心泰颗粒样品,应用中药色谱指纹图谱相似度评价系统(2012版)建立益心泰颗粒指纹图谱共有模式图,并计算相似度,再通过对照品色谱图对共有峰进行指认。结果:通过10批样品的测定,建立益心泰颗粒HPLC指纹图谱,计算得相似度为0.98。共标定31个共有色谱峰,其中4个共有峰19、25、30、31号峰为黄芪药材的专属峰;7个共有峰3、20、21、22、23、24、28号峰为丹参的专属峰;9个共有峰6、7、11、12、13、14、26、27、29号峰为红花的专属峰;6个共有峰8、10、15-18号峰为葶苈子的专属峰;1个共有峰5号峰为泽泻专属峰;1、9号峰为红花、泽泻的共有峰,2号峰为红花、茯苓的共有峰,4号峰为猪苓、丹参的共有峰。并通过对照品色谱图对共有峰进行指认,12、19、21、25、30号峰分别为羟基红花黄色素A、毛蕊异黄酮苷、丹酚酸B、芒柄花素、毛蕊异黄酮。结论:10批样品相似度结果表明该颗粒制备工艺方法稳定可行,同时建立的HPLC指纹图谱方法稳定可靠。
