充分借鉴质量源于设计(QbD)的理念和方法,采用鱼骨分析法对影响替米沙坦氨氯地平双层片关键质量属性(CQA)的处方、过程、设备、环境、人员五大类过程因素进行剖析。运用失败模式和影响分析法(failure mode and effect analysis,FMEA)对...充分借鉴质量源于设计(QbD)的理念和方法,采用鱼骨分析法对影响替米沙坦氨氯地平双层片关键质量属性(CQA)的处方、过程、设备、环境、人员五大类过程因素进行剖析。运用失败模式和影响分析法(failure mode and effect analysis,FMEA)对各因素进行风险评估,并采用Plackett-Burman设计(PBD)对关键工艺参数(CPP)进行筛选。为确定设计空间的控制策略,采用Box-Behnken设计(BBD)对CPP进行优化,建立统计模型,用于分析替米沙坦氨氯地平双层片的制备过程。结果表明,物料温度为37℃、山梨醇粒径为90目、包衣粉用量为11.41%,此条件下自制双层片与原研制剂(Twynsta~?)中替米沙坦溶出曲线的相似因子(f_2)为94.2、有关物质(总杂)为0.90%,期望值能达到1.000。本试验证实通过设置95%置信区间,使设计空间边界的不确定性得到了较好的印证。结果表明,由此设计空间范围内制备的替米沙坦氨氯地平双层片符合拟定标准,且工艺稳定、可行。展开更多
基于质量源于设计(quality by design,QbD)理念,优化胆木提取物的醇沉工艺。在单因素试验的基础上选取试验因素水平,以醇沉体积分数、醇沉前药液浓度、醇沉时间为关键工艺参数(critical process parameters,CPPs),以异长春花苷内酰胺转...基于质量源于设计(quality by design,QbD)理念,优化胆木提取物的醇沉工艺。在单因素试验的基础上选取试验因素水平,以醇沉体积分数、醇沉前药液浓度、醇沉时间为关键工艺参数(critical process parameters,CPPs),以异长春花苷内酰胺转移率与固体去除率的综合评分为关键质量属性(critical quality attributes,CQAs),采用Box-Behnken设计建立CPPs与CQAs之间的数学模型及空间设计,获得最优操作空间并进行验证。实验结果表明最优操作空间为乙醇醇沉体积分数65%~70%,醇沉前药液质量浓度22~27 mg·mL^(-1),醇沉时间12 h。该实验基于QbD理念,将设计空间应用于胆木提取物的醇沉工艺中,为胆木制剂生产过程中的质量控制提供可靠的理论依据,对指导中药工艺研究及工业化生产提供较好的参考价值。展开更多
Quality by Test (Qb T) was the only way to guarantee the quality of drug products before FDA launches current Good Manufacturing Practice (c GMP)[1], which is an approach without clear understanding of the processes. ...Quality by Test (Qb T) was the only way to guarantee the quality of drug products before FDA launches current Good Manufacturing Practice (c GMP)[1], which is an approach without clear understanding of the processes. In order to solve this problem,FDA generalized Quality by Design (QbD) in the field of pharmacy (2)In pharmaceutical industry, Qb D brings cost-efficiency and simplicity of manufacturing process into reality.展开更多
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
Quality by Test was the only way to guarantee quality of drug products before FDA launched current Good Manufacturing Practice. To clearly understand the manufacture processes, FDA generalized Quality by Design(QbD) i...Quality by Test was the only way to guarantee quality of drug products before FDA launched current Good Manufacturing Practice. To clearly understand the manufacture processes, FDA generalized Quality by Design(QbD) in the field of pharmacy, which is based on the thorough understanding of how materials and process parameters affect the quality profile of final products. The application of QbD in drug formulation and process design is based on a good understanding of the sources of variability and the manufacture process. In this paper,the basic knowledge of QbD, the elements of QbD, steps and tools for QbD implementation in pharmaceutics field, including risk assessment, design of experiment, and process analytical technology(PAT), are introduced briefly. Moreover, the concrete applications of QbD in various pharmaceutical related unit operations are summarized and presented.展开更多
Community Question Answering （CQA） websites have greatly facilitated users＇ lives, with an increasing number of people seeking help and exchanging ideas on the Internet. This newlymerged community features two char...Community Question Answering （CQA） websites have greatly facilitated users＇ lives, with an increasing number of people seeking help and exchanging ideas on the Internet. This newlymerged community features two characteristics： social relations and an ask-reply mechanism. As users＇ behaviours and social statuses play a more important role in CQA services than traditional answer retrieving websites, researchers＇ concerns have shifted from the need to passively find existing answers to actively seeking potential reply providers that may give answers in the near future. We analyse datasets derived from an online CQA system named ＂Quora＂, and observed that compared with traditional question answering services, users tend to contribute replies rather than questions for help in the CQA system. Inspired by the findings, we seek ways to evaluate the users＇ ability to offer prompt and reliable help, taking into account activity, authority and social reputation char- acteristics. We propose a hybrid method that is based on a Question-User network and social network using optimised PageRank algorithm. Experimental results show the efficiency of the proposed method for ranking potential answer-providers.展开更多
As part of the method development, the injection volume as a critical quality attribute in fast fused-core chromatography was evaluated. Spilanthol, a pharmaceutically interesting N- alkylamide currently under investi...As part of the method development, the injection volume as a critical quality attribute in fast fused-core chromatography was evaluated. Spilanthol, a pharmaceutically interesting N- alkylamide currently under investigation in our laboratory, was chosen as the model compound. Spilanthol was dissolved in both PBS and MeOH/H20 （70/30, v/v） and subsequently analyzed using a fused-core system hereby selecting five chromatographic characteristics （retention time, area, height, theoretical plates and symmetry factor） as responses. We demonstrated that the injection volume significantly influenced both the qualitative and quantitative performance of fused-core chromatography, a phenomenon which is confounded with the nature of the used sample solvent. From 2 ~tL up to 100 laL injection volume with PBS as solvent, the symmetry factor decreased favorably by 20%. Moreover, the theoretical plates and the quantitative parameters （area and height） increased up to 30%. On the contrary, in this injection volume range, the theoretical plates for the methanol-based samples decreased by more than 60%, while the symmetry factor increased and the height decreased, both by 30%. The injection volume is thus a critical and often overlooked parameter in fused-core method description and validation.展开更多
Contextual question answering （CQA）, in which user information needs are satisfied through an interactive question answering （QA） dialog, has recently attracted more research attention. One challenge is to fuse co...Contextual question answering （CQA）, in which user information needs are satisfied through an interactive question answering （QA） dialog, has recently attracted more research attention. One challenge is to fuse contextual information into the understanding process of relevant questions. In this paper, a discourse structure is proposed to maintain semantic information, and approaches for recognition of relevancy type and fusion of contextual information according to relevancy type are proposed. The system is evaluated on real contextual QA data. The results show that better performance is achieved than a baseline system and almost the same performance as when these contextual phenomena are resolved manually. A detailed evaluation analysis is presented.展开更多
文摘充分借鉴质量源于设计(QbD)的理念和方法,采用鱼骨分析法对影响替米沙坦氨氯地平双层片关键质量属性(CQA)的处方、过程、设备、环境、人员五大类过程因素进行剖析。运用失败模式和影响分析法(failure mode and effect analysis,FMEA)对各因素进行风险评估,并采用Plackett-Burman设计(PBD)对关键工艺参数(CPP)进行筛选。为确定设计空间的控制策略,采用Box-Behnken设计(BBD)对CPP进行优化,建立统计模型,用于分析替米沙坦氨氯地平双层片的制备过程。结果表明,物料温度为37℃、山梨醇粒径为90目、包衣粉用量为11.41%,此条件下自制双层片与原研制剂(Twynsta~?)中替米沙坦溶出曲线的相似因子(f_2)为94.2、有关物质(总杂)为0.90%,期望值能达到1.000。本试验证实通过设置95%置信区间,使设计空间边界的不确定性得到了较好的印证。结果表明,由此设计空间范围内制备的替米沙坦氨氯地平双层片符合拟定标准,且工艺稳定、可行。
文摘基于质量源于设计(quality by design,QbD)理念,优化胆木提取物的醇沉工艺。在单因素试验的基础上选取试验因素水平,以醇沉体积分数、醇沉前药液浓度、醇沉时间为关键工艺参数(critical process parameters,CPPs),以异长春花苷内酰胺转移率与固体去除率的综合评分为关键质量属性(critical quality attributes,CQAs),采用Box-Behnken设计建立CPPs与CQAs之间的数学模型及空间设计,获得最优操作空间并进行验证。实验结果表明最优操作空间为乙醇醇沉体积分数65%~70%,醇沉前药液质量浓度22~27 mg·mL^(-1),醇沉时间12 h。该实验基于QbD理念,将设计空间应用于胆木提取物的醇沉工艺中,为胆木制剂生产过程中的质量控制提供可靠的理论依据,对指导中药工艺研究及工业化生产提供较好的参考价值。
文摘Quality by Test (Qb T) was the only way to guarantee the quality of drug products before FDA launches current Good Manufacturing Practice (c GMP)[1], which is an approach without clear understanding of the processes. In order to solve this problem,FDA generalized Quality by Design (QbD) in the field of pharmacy (2)In pharmaceutical industry, Qb D brings cost-efficiency and simplicity of manufacturing process into reality.
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.
基金financially supported by Talents Project of Liaoning Province, China (LR2013047)
文摘Quality by Test was the only way to guarantee quality of drug products before FDA launched current Good Manufacturing Practice. To clearly understand the manufacture processes, FDA generalized Quality by Design(QbD) in the field of pharmacy, which is based on the thorough understanding of how materials and process parameters affect the quality profile of final products. The application of QbD in drug formulation and process design is based on a good understanding of the sources of variability and the manufacture process. In this paper,the basic knowledge of QbD, the elements of QbD, steps and tools for QbD implementation in pharmaceutics field, including risk assessment, design of experiment, and process analytical technology(PAT), are introduced briefly. Moreover, the concrete applications of QbD in various pharmaceutical related unit operations are summarized and presented.
基金supported by the Fundamental Research Funds for the Central Universitiesthe National Natural Science Foundation of China under Grant No.61271041+2 种基金the National Basic Research Program of China (973 Program) under Grant No.2009CB320504the iCore Integrated Project under Grant No.287708the National Scienceand Technology Major Project under Grants No.2012ZX03005008-001,No.2012ZX03002008
文摘Community Question Answering （CQA） websites have greatly facilitated users＇ lives, with an increasing number of people seeking help and exchanging ideas on the Internet. This newlymerged community features two characteristics： social relations and an ask-reply mechanism. As users＇ behaviours and social statuses play a more important role in CQA services than traditional answer retrieving websites, researchers＇ concerns have shifted from the need to passively find existing answers to actively seeking potential reply providers that may give answers in the near future. We analyse datasets derived from an online CQA system named ＂Quora＂, and observed that compared with traditional question answering services, users tend to contribute replies rather than questions for help in the CQA system. Inspired by the findings, we seek ways to evaluate the users＇ ability to offer prompt and reliable help, taking into account activity, authority and social reputation char- acteristics. We propose a hybrid method that is based on a Question-User network and social network using optimised PageRank algorithm. Experimental results show the efficiency of the proposed method for ranking potential answer-providers.
基金funded by the "Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen)’’ to Jente Boonen(No.091257) and to Matthias D’Hondt(No.101529)
文摘As part of the method development, the injection volume as a critical quality attribute in fast fused-core chromatography was evaluated. Spilanthol, a pharmaceutically interesting N- alkylamide currently under investigation in our laboratory, was chosen as the model compound. Spilanthol was dissolved in both PBS and MeOH/H20 （70/30, v/v） and subsequently analyzed using a fused-core system hereby selecting five chromatographic characteristics （retention time, area, height, theoretical plates and symmetry factor） as responses. We demonstrated that the injection volume significantly influenced both the qualitative and quantitative performance of fused-core chromatography, a phenomenon which is confounded with the nature of the used sample solvent. From 2 ~tL up to 100 laL injection volume with PBS as solvent, the symmetry factor decreased favorably by 20%. Moreover, the theoretical plates and the quantitative parameters （area and height） increased up to 30%. On the contrary, in this injection volume range, the theoretical plates for the methanol-based samples decreased by more than 60%, while the symmetry factor increased and the height decreased, both by 30%. The injection volume is thus a critical and often overlooked parameter in fused-core method description and validation.
文摘Contextual question answering （CQA）, in which user information needs are satisfied through an interactive question answering （QA） dialog, has recently attracted more research attention. One challenge is to fuse contextual information into the understanding process of relevant questions. In this paper, a discourse structure is proposed to maintain semantic information, and approaches for recognition of relevancy type and fusion of contextual information according to relevancy type are proposed. The system is evaluated on real contextual QA data. The results show that better performance is achieved than a baseline system and almost the same performance as when these contextual phenomena are resolved manually. A detailed evaluation analysis is presented.
