Preparation And Properties Study Of New Formulations Of Curcumin

Curcumin(CUR)is a natural polyphenolic anticancer drug with antioxidant,anti-inflammatory and anti-bacterial effects.It is safe even in large doses,but its unstability,insolubility in water and low bioavailability lead to large limitations of clinical applications.It is reported that the pharmaceutical cocrystal is one potential method to improve drug solubility and bioavailability,also,using drug carriers,such as liposome dosage forms,could improve the permeability,in vivo absorption and efficacy of drugs.The main tasks of this study are:(1)Software Gaussian09,Multiwfn were used to calculate the molecular surface electrostatic potential and the difference of intermolecular interaction energyΔE between cocrystals and pure components to evaluate the possibility of CUR cocrystals formation.Simulation results showed that the possibility and correspondingΔE(k J/mol)sorted from largest to smallest was:indole(-6.17)>3,4-dihydroxybenzoic acid(-4.82)>skatole(-4.12)>orcinol(-3.90)>propyl gallate(-3.89)>pyrazinamide(-1.28).CUR-orcinol,CUR-indole cocrystals were successfully prepared by rotary evaporation and grinding methods in acetone/ethanol system.The structure,morphology,solubility,stability,cell toxicity,etc.of cocrystals were characterized by PXRD,TG-DSC,SEM,Raman,FT-IR,UV-vis.Compared with raw CUR,the results showed that the cocrystal products show higher solubility,dissolution rate,stability and cancer cell toxicity.(2)Using cholesterol and egg yolk lecithin as carriers,the complexes of CUR liposomes,which modified with carboxymethyl chitosan,were prepared to enhance the absorption in vivo.Single factor experiments were designed to optimize the formulation and preparation conditions,which were 60 mg of egg yolk lecithin,10 mg of cholesterol,1 mg of CUR,5 m L of hydrated media volume,3 min of ultrasonic time,35 ~oC of hydrated media temperature and 1 h of hydrated time.PXRD,DSC and FT-IR results showed that the drug was successfully encapsulated in liposomes.The liposome products showed good stability and exhibited sustained release to some extent.In vitro cytotoxicity results showed that liposomes had high anticancer toxicity even at low concentrations.The results of this study have certain reference value for the exploration and research of new dosage forms of CUR.