Preparation And Evaluation Of Novel Nano-Amorphous Curcumin

The water solubility of drugs plays a vital role in the dissolution performance of drugs.Poor water solubility is the main factor hindering the clinical application of drugs.Changing the water solubility of drugs is a hot issue in current research.Nanotechnology and amorphous technology are common methods to improve drug solubility.Nanotechnology increases the specific surface area of drug particles by reducing the particle size of drugs,thereby increasing the solubility and dissolution rate of drugs.Amorphous technology improves the bioavailability of drugs by changing the surface free energy of drugs.In this paper,nanotechnology and amorphous organic combination of two techniques to improve the water solubility of drugs in order to improve drug solubility.In this paper,amorphous drugs were prepared by quenching method,amorphous drugs were further processed by grinding method,and nano-amorphous drugs were prepared by technology combination.The effects of different types of polymers and different contents of the same polymer on the microscopic molecular structure,intermolecular interaction form,crystal form change,in vitro dissolution and stability of nano-amorphous drugs were investigated,and the parameters that had great influence on nano-amorphous drugs in the preparation process were optimized to obtain the best preparation process.Experiments showed that the crystallinity of amorphous curcumin prepared by polyvinylpyrrolidone or povidone decreased,and some or all of them were converted into amorphous state.The optimum wet grinding process for preparing nano-amorphous drug after response surface optimization was as follows : drug concentration 2 %,grinding time 130 min,drug and polymer ratio 0.5.The in vitro dissolution of amorphous curcumin was significantly different from that of curcumin nanosuspension or amorphous curcumin,which proved that the combination of reducing particle size and crystallinity had a synergistic effect on drug dissolution and increased drug solubility.The effects of drug particle size,crystallinity,and the amount of SDS on the in vitro dissolution efficiency of nano-amorphous curcumin were analyzed by response surface technology.According to the F value of the model,the crystallinity of the drug had the most significant effect on the in vitro dissolution efficiency of the drug at 0-3min,followed by the particle size of the drug and the amount of SDS.According to the P value,all three had a significant effect on the in vitro dissolution efficiency of the drug.In the 3-60 min of in vitro dissolution,the F value of drug crystallinity is still the largest,which proves that the influence of drug crystallinity on the in vitro dissolution efficiency of drugs is still the most significant at this stage,but according to the P value,the drug particle size no longer has a significant effect on the in vitro dissolution efficiency.Nano-amorphous curcumin was solidified by freeze-drying technology,and mannitol and sucrose were selected as candidate materials for curing protective agent.The particle size of the solidified sample prepared by using mannitol as curing protective agent increased only within 50 nm after redispersion,and the maximum dissolution in vitro decreased only within 5 %.There was almost no change in the redispersed particle size and in vitro dissolution after 60 days of storage.The particle size of the solidified sample prepared with sucrose as curing protective agent increased by more than 100 nm after redispersion,and the in vitro dissolution decreased by more than 15 %.After 60 days of storage,the in vitro dissolution decreased by 20 %compared with that before storage.Experiments confirmed that mannitol as a curing protective agent can keep the sample stable for a long time.The nano-amorphous curcumin was prepared into tablets,and the powder direct compression process was selected according to the drug properties.The composition of tablet excipients was optimized by orthogonal experiment.By comparing the in vitro dissolution curves before and after tableting,it was found that after the preparation of the tablet,the dissolution of the drug was affected by the disintegration of the tablet,and the dissolution changed slightly in the early stage of dissolution,but the maximum in vitro dissolution of the tablet was consistent with that before tableting.The experiment proved that the preparation of the tablet did not affect the maximum in vitro dissolution of the drug.