Study On Separation Process Of Antidiabetic Drug Acarbose With Cation Exchange Chromatography

Acarbose is a potent ca-glucosidase inhibitor,and possesses beneficial effects on postprandial hyperglycaemia,hyperlipidaemia and fasting blood-glucose.Thus,it is widely used as the active pharmaceutical ingredient(API)of some commercial antidiabetic drugs.Despite that many methods have been documented to separate the acarbose from fermentation broths,theoretical study on acarbose adsorption on strong-acid cation-exchange resin is not comprehensive.The main purpose of this research is to establish a separation prpcess for acarbose from fermentation broth using cation exchange chromatography.Acarbose adsorption on three types of strong-acid cation-exchange resins was initially evaluated.Acarbose adsorption on strong-acid cation-exchange 001x4,SR-1 and PT151 resins are spontaneous,endothermic.Chemisorption and ion exchange mechanism participate in acarbose adsorption,and the isotherms data were well fit to the Langmuir model.The maximal static adsorption capacity increased with increasing the temperature.Moreover,adsorption kinetics follows the pseudo second-order model.Effect of initial acarbose concentration,flow rate and bed height on the breakthrough of acarbose in fixed bed was studied.The dynamics model that combined the Langmuir isotherm and linear mass-transfer equation was developed to predict the breakthrough behavior of acarbose adsorption in a fixed bed packed with strong-acid cation-exchange 001X4,SR-1 and PT151 resins.Two important parameters,the half breakthrough time(t1/2)and the mass-transfer coefficients(KLa)in the model were obtained from linear fitting of the model to experimental breakthrough data.Compared with the Yoon-Nelson kinetic models,it was found that the Yoon-Nelson model described acarbose adsorption behavior in the given system more reasonably than the dynamics model.Moreover,50.0 mM NH3·H2O solution was a preferential eluant for acarbose desorption in a step-wise elution manner.Based on the above outcomes and experimental attempts,a new separation process was developed for acarbose from A.utahensis ZJB-08196 fermentation broth.It consists of 3 steps:deproteinization with resin HZ830,decoloring with resin WD-6 and cation exchange chromatography with strong-acid cation exchanger 001X4,SR-1 and PT151 resins.During the pretreantment process of A.utahensis ZJB-08196 fermentation broth,proteins and pigments in the supernatant were removed by resins HZ830 and WD-6,In order to reduce impurities interference for column chromatography.After strong acid cation exchange chromatography packed with resin PT151 and freeze drying,the acarbose purity reached 95.0%(w/w),with an overall recovery of 67.0%(w/w).