The Study Of Loratadine Crystallization Process

Loratadine is a kind of anti-allergic drug.Because of its high efficiency,quick-impact,powerful characteristic and the safety for using,it is widely used for the treatment of different allergic skin diseases,such as asthma,allergic rhinitis,hay fever and so on.However,at present,the study of loratadine mostly concentrated on the synthetic process and preparation research.There are few studies about its solid-liquid equilibrium and crystallization process.This paper systematically studied the crystallization process of loratadine through experimental study and theoretical analysis.Laser dynamic method is used to determine the solubility data of loratadine in ten kinds of pure solvent(methanol,ethanol,isopropanol,n-propanol,n-butanol,n-pentanol,acetonitrile,acetone,ethyl acetate and DMF)and two kinds of mixed solvent(methanol + acetonitrile,amyl alcohol + acetonitrile).In all these selected solvents,the solubility of loratadine increases with the increasing of temperature.The solubility order in pure solvents is n-pentanol>n-butanol,methanol>n-propanol>DMF>ethanol,ethyl acetate>acetone>i-propanol>acetonitrile.The solubility of loratadine increases first and then decreases with the increasing mole fraction of methanol or n-pentanol separately in these two different binary solvent mixtures.The modified Apelblat equation,three parameters van't Hoff equation and Jouyban-Acree model are applied to correlate the experimental solubility in different solvents,and they all correlated well.On this basis,the thermodynamic functions of loratadine dissolving in different solvents are studied.In addition,the metastable zone of loratadine in ethanol is studied.Analysis methods such as XRPD,FT-IR,DSC,TG-DTG were adopted to characterize and analyze loratadine.By cooling crystallization process,the crystal of loratadine crystallized from ethanol solvent.According to the XRPD spectra of the crystal,the crystal structure was analyzed by the Material Studio software and the crystal habit was forecasted by different models.With solubility data of loratadine in ethanol solvent as the foundation,controlling variables to investigate the influence of different operating conditions(initial concentration,agitation speed,cooling rate,final temperature,crystal growing time,whether to add the seed crystal)on crystal habit and particle size of crystal products.Finally,the best process condition is determined as that the initial concentration is 26.91%,the agitation speed is 200 rpm,the cooling rate is 0.8?/min,final temperature is 10 ?,keeping crystal time for 1.5 h and adding seed crystal.According to the study of solubility and crystallization process,this project provides theoretical basis for the production of loratadine in industrial field.