Studies On Clarity Control Of Sheng-mai-Yin(Dangshenfang) Based On The Concept Of QbD

Turbidity and precipitate usually occur in production and storage of liquid preparations of Chinese medicine,it was called clarity problem.This problem has a serious impact on the safety,effectiveness and appearance of the final product.The concept of quality by design(QbD)is to establish a design space in the implementation of production process.In the design space,quality of product will be stable even under the condition of some parameters changed.Shengmai Yin(Dangshenfang)is a widely used prescription which made of Radix Codonopsis,Radix Ophiopogonis and Fructus Schisandrae.Its production steps including extraction by water,precipitation by ethanol and deposition with water.Clarity problem is a big problem exsists in Shengmai Yin(Dangshenfang).In order to control the occurrence of clarity problem,concept of QbD was applied to the study of three steps of production in this research.The contents mainly include:Study on the step of extraction.Risk assessment was used to get the critical quality attributes(CQAs)of extraction process,they are dry matter extracted,active ingredient contents in the concentrated liquid,turbidity and protein contents.The critical process parameters(CPPs),the quantity ratio of water and material,extraction time and extraction times also obtained.Furthermore,A mathematical model of extraction process based on single factor experiment was developed by Box-Behnken Design.The effect of different extraction processes on clarities of intermediates and products were investigated.Finally,design space is obtained: extract twice,the quantity ratio of water and material range in 11.5-12.8 and extraction time range in 2.8-3.6 h.Study on step of ethanol precipitation.Taking the ratio of dry matter removal,recovery of three marker compounds,ratio of protein removal and turbidity of product as the CQAs,we use Plackett-Burman design to obtain the CPPs which are relative density of concentrated liquid,concentration of ethanol and amount of ethanol.Then,Box-Behnken design was used to establish a mathematical model of ethanol precipitation process.At last,design space was got which includesthe ratio of ethanol to extract is 1.8,relative density of concentrated liquid range in1.28-1.33 and ethanol concentration range in 87.5-95.0%.Study on step of water precipitation.Turbidity,protein content,relative density and the active components recovery are regarded asCQAs.Plackett-Burman design was applied to obtain CPPs,which are the relative density of thick paste,water added amount and pH of products.Box-Behnken design was used to establish a mathematical model of water precipitation process.The obtained design space includes:when pH of products is 4,relative density of thick paste range in1.33-1.37 and water added amount range in 4.1-4.6.The result showed a good products with stable and good quality can be obtained when produced in the above design space.