Study On Preparation Of Curcumin Sustained-Release Solid Dispersion By Hot Melt Extrusion

Curcumin is an acidic phenolic compound extracted from the rhizome of Curcuma longa L.,which is mianly used for anti-tumor,anti-inflammatory,anti-bacterial,anti-fibrosis and anti-tumor properties,depressive,hypolipidemic and other pharmacological effects.However,curcumin has low water solubility,which is only 7.8 μg·mL-1 in water.Curcumin has a short half-life and a fast elimination rate in the body,resulting in low oral bioavailability of curcumin,which limits the clinical application of curcumin.The technology of solid dispersion is often used to improve the solubility of poorly soluble drugs,and can be used to delay the release of drugs by the use of waterinsoluble carriers.Hot melt extrusion technology is a new type of solid dispersion preparation technology.It has the advantages of simple operation,continuous operation,and no need to use organic solvents.In recent years,it has been used to improve the solubility and bioavailability of poorly soluble drugs.A solid dispersion was prepared by hot melt extrusion technology to improve the solubility of curcumin.Water-insoluble carriers were selected to delay release of drug.Curcumin sustainedrelease solid dispersion was prepared by applying a hot melt extrusion technique,to improve the solubility of drug and delay the release of drug.The HPLC method for the determination of curcumin was established and the method was verified.At the same time,the in vitro release method of curcumin was established,and the equilibrium solubility of curcumin were of curcumin was investigated.Solubility parameter method and Flory-Huggins interaction parameter method were used to judge the compatibility of the drug with the carrier to screen the vector.The melting point or glass transition temperature and thermal decomposition temperature of the drug and excipients were investigated by thermal analysis.The drug content,crystallinity,release curve and similarity factor f2 were used as evaluation indexes to investigate the effects of carrier ratio,drug loading ratio,porogen type and porogen dosage on drug release of sustained-release solid dispersion.The optimal prescription was screened by orthogonal experiment.The single factor test was used to screen the optimal process parameters,and the optimal formulation process was as follows:carrier ratio RS:RL=1:3,drug loading ratio was 1:6,HPC was used as porogen,and the amount was auxiliary material.40%,the barrel temperature was 145℃,the screw speed was 80 rpm.The sample was cooled in liquid nitrogen,pulverized and ground through an 80 mesh sieve and a 100 mesh sieve,and the portion having a mesh size of 80 mesh was retainedThe in vitro dissolution behavior of the curcumin sustained-release solid dispersion was investigated,which shows a good sustained release effect.The equilibrium solubility of the curcumin sustained-release solid dispersion was determined.The results showed that the equilibrium solubility of solid dispersion was increased compared with the bulk drug.The solid phase was identified by DSC,XRD and FTIR,and the results showed that curcumin was present in the solid dispersion in an amorphous state.The influencing factors test results show that the solid dispersion is unstable under strong light and high humidity environment and needs to be stored in the dark.The release mechanism of curcumin was studied,and the release curve was fitted to the Ritger-Peppas release model.The release process of curcumin sustained-release solid dispersion was a diffusion and dissolution coexisting effect.The in vivo pharmacokinetic study of the curcumin sustained-release solid dispersion prepared by the optimal formulation process was established,and the plasma concentration of curcumin in SD rats was determined by liquid chromatography-mass spectrometry(UPLCMS/MS).Validation,SD male rats were randomly divided into two groups:Curcumin drug group(CUR),curcumin sustained-release solid dispersion group(CUR SD).UPLC-MS/MS was used to determine blood concentration,and fit with a non-compartmental model.The results showed that compared with the drug substance,the Cmax and AUC0-t of curcumin in the sustained solid dispersion were significantly improved,and the bioavailability of curcumin was significantly increased.In this paper,the curcumin sustained-release solid dispersion was successfully prepared by using the hot melt extrusion technology with Eudragit RS and Eudragit RL as carriers,which increased the solubility of the drug and delayed the release of the drug.