Process Parameters Investigation On The Preparation Of Microcapsules By Supercritical Fluid Extraction Of Emulsions

Supercritical fluid extraction of emulsions combines supercritical fluid technology and emulsion solvent evaporation technology.The organic solvent on the oil phased of double emulsion is been removed by using the excellent solubility of supercritical carbon dioxide.Compared with the traditional method,morphology controllable microcapsules without organic solvent residue can successfully obtained.In order to make the microencapsulation technology have better apply in the pharmaceutical industry,this study investigated the preparation processing of co-delivery microcapsules using supercritical fluid extraction of emulsions technology.This study used propranolol hydrochloride as hydrophilic drug model,nitrendipine as hydrophobic drug model,Span80 as lipophilic surfactant,polyvinyl alcohol as hydrophilic surfactant,polycaprolactone as cliff material,and ethyl acetate and dichloromethane as organic solvent of oil phase.In this study,the encapsulation efficiency,the solvent residual and the morphology of microcapsules were been studied.The following works have been done:(1)A kind of stable water-in-oil-in-water double emulsion was preparation.The propranolol hydrochloride in the inner aqueous phase,nitrendipine in the oil phase,and using polyvinyl alcohol as hydrophilic surfactant.When using both ethyl acetate and dichloromethane(ethyl acetate: dichloromethane = 3:1)as organic solvent of oil phase,concentration of Span80 was 0.3 mol/L and concentration of polycaprolactone was 0.6 g can obtain double emulsion having a high encapsulation efficiency and drug loading rate.(2)Using double emulsions,which have high encapsulation efficiency as model emulsion to produce co-delivery microcapsules by supercritical fluid extraction of emulsion,a kind of microcapsules which have high encapsulation efficiency and drug loading rate,low solvent residual and good morphology was been produced,when the pressure of supercritical carbon dioxide was 8 MPa and the temperature was 50℃.Hydrophilic drug has a more serious initial release while hydrophobic drugs not.(3)Analyzed the mechanism of microcapsules granulation,and the influencing factors of microcapsules morphology were the formula of model emulsion.Moreover,the principle of solvent removal was also been studied.A simple mass transfer model of organic solvent,water and carbon dioxide was established.