| Objective: 1.Establish a UPLC methodology for quantitative analysis of drug loading and in vitro release of GA-mPEG-PLGA microspheres.2.Screening the best preparation method for GA microspheres,selecting organic phase solvents and continuous phase surfactants.The single factor method was used to investigate the key material properties and key process parameters for preparing GA-mPEG-PLGA microspheres based on micro mixers.4.The curing process of GA-mPEG-PLGA microspheres was analyzed by Raman spectroscopy and FBRM to reveal the formation process of mPEGPLGA microspheres.Methods: 1.Establish a quantitative UPLC analysis method for drug loading and in vitro release of GA microspheres,detect the wavelength through ultraviolet spectroscopy,and conduct methodological studies;2.Prepare GA-PLGA microspheres,formulate a preparation plan based on the physical characteristics of GA,and screen with drug loading as an indicator;Using drug loading as an indicator,the best solvent for organic phase and the best surfactant for continuous phase were selected.3.Prepare GA-mPEG-PLGA microspheres,screen the key material properties of mPEGPLGA based on drug loading as an indicator,prepare GA-mPEG-PLGA microspheres based on a micro mixer,and screen the key process parameters and key material properties.4.Establish a Raman spectral linear model,and combine with FBRM analysis to analyze the curing process of GA-mPEG-PLGA microspheres prepared by the best process using the micro mixer method,revealing the formation process of GA-mPEG-PLGA microspheres,and standardizing the microspheres.Result: The drug loading analysis and in vitro release quantitative analysis methods of GA microspheres are reliable,and their specificity,precision,repeatability,and accuracy meet acceptance standards.Through screening,it can be seen that the double emulsion solvent evaporation method with GA aqueous solution as the drug phase has the highest drug loading,the optimal solvent for the organic phase is DCM,and the continuous phase surfactant is PVA.When the mass ratio of mPEG/PLGA is 1:19,the drug loading is the highest.The increase in the proportion of lactic acid in the PLGA terminal slows the curing rate,increases the escape of the drug phase,and decreases the drug loading.The microspheres prepared by the micro mixer exhibit a narrow particle size distribution.With the increase of polymer phase concentration,the encapsulation efficiency increases,while with the increase of surface phase concentration from 0.5% to 2%,the encapsulation efficiency decreases.Raman spectroscopy shows that as the organic solvent evaporates during the curing process,the DCM concentration decreases and the polymer concentration increases.In addition,it can be found that the concentrations of DCM and mPEG-PLGA do not change after 90 minutes,indicating that the end point of curing is 90 minutes.FBRM test showed that the particle size gradually increased from 25 μ m to 28 μ m from 0 min to 120 min,and significantly decreased from 120 min to 130 min,which indicated that with the evaporation of organic solvent,lotion droplets became microspheres,and the particle size did not change from 130 min to 300 min.Conclusion: The established UPLC method is accurate and reliable,and can be used for quantitative analysis of drug loading and in vitro release of GA microspheres.GA-mPEG-PLGA microspheres can be prepared continuously/semi continuously based on a micro mixer,with high drug loading and low cost.3.In the process of microsphere curing,firstly,the hydrophilic end of mPEG PLGA is stretched into an aqueous phase and adsorbed water,resulting in a larger hydrate particle size.With the evaporation of organic solvent,the lotion droplets become microspheres.The amphiphilic nature of mPEG PLGA acts as an emulsifier,which can reduce the interfacial tension.Since the water molecule combines with the mPEG chain,the PLGA chain quickly and directly combines with the core of the droplets.After the precipitation of the PLGA chain,Copolymers lose their amphiphilic properties. |
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