The Polymorphy Studies Of L-glutamic Acid Under Droplet-microfluidic System

Different polymorphs usually have significantly different physicochemical properties,which affect the efficacy of a drug.Thus polymorphism has become a hot topic for both academic researches and pharmaceutical industries,and the study of polymorphy is an essential part in drug research and development.Microfluidic system has significant advantages in some aspects,such as continuous operation,accurate temperature control,a small amount of raw material consumption.It has become a new tool for crystallization researches now.L-glutamic acid is one of the basic amino acids.It has two crystal forms,which are the metastable ? form and the stable ? form.Droplet-microfluidic system was used to investigate polymorphs of L-gluatamic acid in this work.The details were as followed.The solubility of L-glutamic acid stable form in pure water was measured by static method,and the datum were correlated by empirical equation.The solubility of stable form in solvent mixture of ethanol + water solution and acetone + water solution was measured,and the effect of solution composition was investigated.Moreover,the metastable zone width of L-glutamic acid in pure water and ethanol + water solution was studied by droplet-microfludic system.The trend of date obtained by this method was consistent with that of using traditional methods.It proves that microfluidic method is an economic and feasible method to measure the metastable zone width.The space scale of crystallization and the interface effect can affect nucleation and growth of crystals.The droplet-microfluidic method was used to investigate the effect of supersaturation,crystallization temperature,droplet size,microchannels metarials and solvents composition on L-glutamic acid polymorphism in microscale,and the nucleation mechanism of different crystallization conditions was discussed.What's more,microscope and powder X-ray diffraction(PXRD)were used to observe and analyze crystals.The droplet formation mechanisms for T-shape microchannels and flow focusing microchannels were simulated by CFD using two-dimension models.In addition,CFD was used to investigate the effects of continuous phase specific heat capacity,continuous phase thermal conductivity,miacrochannel materials and droplet size on temperature evolution of the static liquid-liquid two-phase.Simulation results demonstrate that the heat transfer rate between the micro-droplets and the medium inside the channels is very fast.So it is easy to realize the accurate and rapid control of the crystallization temperature in the droplets.