In this work, 10 batches of Salvia miltiorrhiza concentrate were prepared and purified with ethanol precipitation process. Dry matter content, pH value, conductivity and water content of the concentrates and supernata...In this work, 10 batches of Salvia miltiorrhiza concentrate were prepared and purified with ethanol precipitation process. Dry matter content, pH value, conductivity and water content of the concentrates and supernatants were all determined. When more ethanol was used in ethanol precipitation, the pH value of the supernatant generally increased, but dry matter content, water content, and the conductivity decreased. Multivariate linear models were built with the most determination coefficient values greater than 0.7. More than 80% of stachyose was removed in the ethanol precipitation process. The removal rate of fructose, raffinose and sucrose were all higher than 30%. When ethanol addition amount increased, the purity of phenolic acids in the supernatant increased, but the retention of lithosperimic acid and salvianolic acid B decreased. The conductivity and pH value of concentrated extract show relatively small influences on ethanol precipitation indices. When fructose, raffinose, or stachyose contents in the concentrated extract were high, the retention rate of phenolic acids tends to be low on most occasions. The purity and retention rate of phenolic acids in the supernatants were also affected by the purity of phenolic acids in the concentrated. The sugar contents in the concentrate are suggested to be monitored in industry because they significantly affect ethanol precipitation process indices.展开更多
The present study was designed to determine the relationships between the performance of ethanol precipitation and seven process parameters in the ethanol precipitation process of Re Du Ning Injections,including conce...The present study was designed to determine the relationships between the performance of ethanol precipitation and seven process parameters in the ethanol precipitation process of Re Du Ning Injections,including concentrate density,concentrate temperature,ethanol content,flow rate and stir rate in the addition of ethanol,precipitation time,and precipitation temperature.Under the experimental and simulated production conditions,a series of precipitated resultants were prepared by changing these variables one by one,and then examined by HPLC fingerprint analyses.Different from the traditional evaluation model based on single or a few constituents,the fingerprint data of every parameter fluctuation test was processed with Principal Component Analysis(PCA)to comprehensively assess the performance of ethanol precipitation.Our results showed that concentrate density,ethanol content,and precipitation time were the most important parameters that influence the recovery of active compounds in precipitation resultants.The present study would provide some reference for pharmaceutical scientists engaged in research on pharmaceutical process optimization and help pharmaceutical enterprises adapt a scientific and reasonable cost-effective approach to ensure the batch-to-batch quality consistency of the final products.展开更多
Objective:Critical process parameters(CPPs)identification is an important step of the implementation of quality by design(Qb D)concept.There are many CPP identification methods,such as risk analysis method,sensitivity...Objective:Critical process parameters(CPPs)identification is an important step of the implementation of quality by design(Qb D)concept.There are many CPP identification methods,such as risk analysis method,sensitivity analysis method,multiple linear regression method,standard partial regression coefficient(SPRC)method,and so on.The SPRC method can consider multiple process critical quality attributes(CQAs)simultaneously,but the determination of CPP number is subjective.Therefore,new CPP identification method is still required.Methods:The manufacturing process of Astragali Radix extract,which contained water reflux extraction,concentration,and ethanol precipitation,was used as an example.First,the multiple process CQAs were determined to be the yield of pigment,dry matter,sugars,and active ingredients.Second,the potential CPPs were determined by a knowledge organization method.Plackett-Burman designed experiments were then performed.A weighted determination coefficient(R2 w)method was presented to identify CPPs.In this method,the importance of different CQAs was considered.Process parameters were removed one-by-one according to their importance index.The decrease in R2 wwas used to characterize the importance of the removed parameter.If the decrease of R2 wwas less than a preset threshold,the removed parameter was not a CPP.Results:During the manufacturing process of Astragali Radix extract,the potential CPPs determined by the knowledge organization method were water consumption,reflux extraction time,extraction frequency,ethanol content,ethanol consumption,and concentration endpoint.Reflux extraction time,the first ethanol consumption,the second ethanol consumption,and the second ethanol precipitation refrigeration temperature were found to be CPPs using the weighted determination coefficient method with the threshold of 10%.Conclusion:Using the weighted determination coefficient method,CPPs can be determined with all the CQAs considered based on their importance.The determination of CPP number is more objective compared with the SPRC method.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
文摘In this work, 10 batches of Salvia miltiorrhiza concentrate were prepared and purified with ethanol precipitation process. Dry matter content, pH value, conductivity and water content of the concentrates and supernatants were all determined. When more ethanol was used in ethanol precipitation, the pH value of the supernatant generally increased, but dry matter content, water content, and the conductivity decreased. Multivariate linear models were built with the most determination coefficient values greater than 0.7. More than 80% of stachyose was removed in the ethanol precipitation process. The removal rate of fructose, raffinose and sucrose were all higher than 30%. When ethanol addition amount increased, the purity of phenolic acids in the supernatant increased, but the retention of lithosperimic acid and salvianolic acid B decreased. The conductivity and pH value of concentrated extract show relatively small influences on ethanol precipitation indices. When fructose, raffinose, or stachyose contents in the concentrated extract were high, the retention rate of phenolic acids tends to be low on most occasions. The purity and retention rate of phenolic acids in the supernatants were also affected by the purity of phenolic acids in the concentrated. The sugar contents in the concentrate are suggested to be monitored in industry because they significantly affect ethanol precipitation process indices.
基金supported by 973 Project from the Ministry of Science and Technology of China(No.2010 CB735604)
文摘The present study was designed to determine the relationships between the performance of ethanol precipitation and seven process parameters in the ethanol precipitation process of Re Du Ning Injections,including concentrate density,concentrate temperature,ethanol content,flow rate and stir rate in the addition of ethanol,precipitation time,and precipitation temperature.Under the experimental and simulated production conditions,a series of precipitated resultants were prepared by changing these variables one by one,and then examined by HPLC fingerprint analyses.Different from the traditional evaluation model based on single or a few constituents,the fingerprint data of every parameter fluctuation test was processed with Principal Component Analysis(PCA)to comprehensively assess the performance of ethanol precipitation.Our results showed that concentrate density,ethanol content,and precipitation time were the most important parameters that influence the recovery of active compounds in precipitation resultants.The present study would provide some reference for pharmaceutical scientists engaged in research on pharmaceutical process optimization and help pharmaceutical enterprises adapt a scientific and reasonable cost-effective approach to ensure the batch-to-batch quality consistency of the final products.
基金the support of National Project for Standardization of Chinese Materia Medica(ZYBZH-C-GD-04)Student Research Training Program of College of Pharmaceutical Sciences of Zhejiang University(Y36023)。
文摘Objective:Critical process parameters(CPPs)identification is an important step of the implementation of quality by design(Qb D)concept.There are many CPP identification methods,such as risk analysis method,sensitivity analysis method,multiple linear regression method,standard partial regression coefficient(SPRC)method,and so on.The SPRC method can consider multiple process critical quality attributes(CQAs)simultaneously,but the determination of CPP number is subjective.Therefore,new CPP identification method is still required.Methods:The manufacturing process of Astragali Radix extract,which contained water reflux extraction,concentration,and ethanol precipitation,was used as an example.First,the multiple process CQAs were determined to be the yield of pigment,dry matter,sugars,and active ingredients.Second,the potential CPPs were determined by a knowledge organization method.Plackett-Burman designed experiments were then performed.A weighted determination coefficient(R2 w)method was presented to identify CPPs.In this method,the importance of different CQAs was considered.Process parameters were removed one-by-one according to their importance index.The decrease in R2 wwas used to characterize the importance of the removed parameter.If the decrease of R2 wwas less than a preset threshold,the removed parameter was not a CPP.Results:During the manufacturing process of Astragali Radix extract,the potential CPPs determined by the knowledge organization method were water consumption,reflux extraction time,extraction frequency,ethanol content,ethanol consumption,and concentration endpoint.Reflux extraction time,the first ethanol consumption,the second ethanol consumption,and the second ethanol precipitation refrigeration temperature were found to be CPPs using the weighted determination coefficient method with the threshold of 10%.Conclusion:Using the weighted determination coefficient method,CPPs can be determined with all the CQAs considered based on their importance.The determination of CPP number is more objective compared with the SPRC method.
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。
