Experimental instructional design for quantitative calculation of the molecular state of rosmarinic acid using nanofiltration mass transfer model
[Objective]The pharmaceutical process's component transmission behavior is determined by its molecular state.Currently,infrared spectroscopy,nuclear magnetic resonance,differential thermal analysis,high-resolution scanning electron microscopy,and other techniques are used to analyze the molecular state of pharmacological components.Nevertheless,to apply the aforementioned technologies,the components must be isolated from the original solution.Using the detection principle,a qualitative analysis of the component status can be produced,but the precise ratio of ionic,molecular,and other states cannot be determined.In this work,a teaching experiment was designed for the quantitative calculation of the molecular state of rosmarinic acid using a nanofiltration mass transfer model.[Methods]Using the theory that"nanofiltration mass transfer coefficient can represent the difficulty of components passing through nanofiltration membrane pores,and is a manifestation of comprehensive separation of multiple states of existence,"this study developed an experimental teaching program based on the nanofiltration mass transfer model for the quantitative analysis of drug ingredient molecular states.Given that rosmarinic acid has a pKa of 4.01,a 5％hydrochloric acid solution was used,and the mass concentration was adjusted to 0.210 mg/mL.The pH of the rosmarinic acid monomer component solution was 2.01,implying that 99％of the molecular state of rosmarinic acid was present.The rosmarinic acid solution was put in the liquid storage tank,and the system pressures of the nanofiltration apparatus were changed to 0.6,0.8,1.0,1.2,and 1.4 MPa,respectively.The nanofiltration liquid and membrane flux(Jv)were then collected at an appropriate pressure.Using high-performance liquid chromatography,the rosmarinic acid solution and filtrate were identified,and the retention rate(R)was computed.The linear equation of ln[(l-R)Jv/R]and the nanofiltration mass transfer coefficient of rosmarinic acid(k)were fitted using the correlation among k and R and Jv.Subsequently,the power function equations for k and rosmarinic acid concentration(C)were fitted,and the extracted liquid of Salvia miltiorrhiza was separated using nanofiltration,with the proportion of rosmarinic acid molecular states determined using the power function equations of the concentration and mass transfer coefficient of this monomeric component.Furthermore,the relationship between the transfer rate and the component molecular states during the alcohol precipitation,resin adsorption,clarity filtration,concentration,and drying processes was investigated.[Results]Rosmarinic acid had a molecular proportion of 33.62％in Salvia miltiorrhiza extract.Rosmarinic acid's solubility in ethanol solution fell as its molecular proportion dropped,and it was easily adsorbed by polysaccharide,protein,and colloid components during alcohol precipitation,resulting in a decrease in alcohol precipitation transfer rate.Rosmarinic acid was difficult to adsorb on the surface of the macroporous resin,and the transfer rate increased as the aqueous solution flowed out.Rosmarinic acid had a substantial interfacial adsorption impact on the surface of the microfiltration membrane,leading to component loss.The results showed that the existence of rosmarinic acid had a significant effect on the component transfer rate in the pharmaceutical process,which aided in the standardization of the manufacturing process.[Conclusions]This experiment combined important pharmaceutical issues with scientific research to feed teaching,develop students'scientific research literacy and practical ability,and realize the collaborative improvement of scientific research application and teaching expansion.
molecular statenanofiltrationChinese pharmaceutical manufacturingmass transfer modelrosmarinic acid
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