Screening And Application On The Techonlogy And Prescription Of Microcapsules By Phase Separation

At home and abroad, Microencapsulated technology is a new technology. It is an important direction of development in the field of pharmaceutical preparations in recent years. It has showed a lot of special advantages for improving the performance and effect of the drug since obtained. One method of drug microencapsulation is phase separation, including simple coacervation and complex coacervaion. The equipment used by phase separation is simple, the polymer materials are variety, many kinds of drugs can be microencapsulated. But there are many influencing factors, too. And its reproducibility is not so good. In this paper, two different types of drugs are chosen to be microencapsulated by phase separation method, in order to have a more comprehensive study about prescription and process of phase separation.Florfenicol was chosen to be the model of insoluble solid drug. First, single factor experiments of complex coacervation were done to determine the approximate range of influencing factors:the proportion of gelatin and gum arabic was1:1, the material concentration was2%-3%, the pH of microencapsulation was about4.0, the best ratio of drug and material was about1:2, stirring speed was about500r/min and the temperature of microencapsulation was45-55℃; the wetting agent AEO9adding conditions were obtained by the orthogonal experiment:the amount of AEO9was0.6ml, the ratio of drug and material was set at1:3; Transglutaminase was chosen to be curing agent, curing conditions of Transglutaminase were obtained by the orthogonal experiment:The amount of Transglutaminase was2.0g, curing pH was5.4, time of curing was1h, aging time was24h; central composite design-response surface method was used to optimized the technology and prescription conditions of preparation of microcapsules by complex coacervation:the concentration of material was2.2%, the microencapsulation pH was3.9, stirring speed was450r/min. The result had good reproducibility. And the prepared microcapsules had a good sustained release in vitro.Then, the single factor experiments of single coacervation were done to determine the approximate range of influencing factors:the concentration of material was5%, encysted pH was4.0,the concentration of sodium sulfate solution was25%, the ratio of drug and material was1:2-1:5, the stirring speed was500-700r/min and the encysted temperature was45-55℃; wetting agent and curing conditions were unchanged; central composite design-response surface method was used to optimized the technology and prescription conditions of preparation of microcapsules by single coacervation:drugs accounted for3.75%of the material, the encysted pH was4.8, stirring speed was615r/min. The particle size of the prepared microcapsules was40-50μm, the encapsulation efficiency could up to57.12%. The result had good reproducibility. And the prepared microcapsulaes had a good sustained release in vitro.Vitamin A palmitate was chosen to be the model of insoluble Liquid drug. First, screening the preparation conditions of the emulsion of vitamin A palmitate:speed of stirring was1200r/min, and stirring time was10min; verify the optimized conditions of complex coacervation; the particle size of Vitamin A palmitate microcapsules was30-40μm, encapsulation efficiency can up to68.9%, proving that the method of complex coacervation had reproducibility. Selecting the conditions of fluidized bed drying:the gun position was from the fluidized material10-llcm,the air intake pressure was1MPa, the spray pressure was1MPa, the spray liquid flow rate was O.lml/min, and the fluidized bed temperature was60℃. The microcapsules obtained were dry, adhesions, no deformation. The experiments of light stability and thermal stability of the dried microcapsules were done to show that the products had good stability.Then, the emulsifying conditions were unchanged, verify the optimized conditions of single coacervation; the particle size of Vitamin A palmitate microcapsules was30-40μm, the encapsulation efficiency can up to63.8%, the result proving that the method of single coacervation had reproducibility. The drying conditions of the microcapsules were unchanged; the experiments of light stability and thermal stability of the dried microcapsules were done, showing that the products had good stability. The experiments show that, to different drugs, the prescription and technology conditions of microencapsulation by phase separation were controllable, and the products were stable.