Quantified Control Of The Formulation And Process Parameters To Sustained Release Pellets Prepared By Fluidized Bed

Dimethyl Fumarate(DMF) was mainly used as fungistats of food and shoes in industry. It was efficient as fungistats. It was used to treat multiple sclerosis in clinieal. The Tmax of DMF was 2-2.5 hours. It was strong and sharp in flavor, can cause those adverse reactions such as flushing, stomachache, diarrhea, nausea and so on. So it was suitable to be made into sustained- release preparation. Sustained-release pellets of DMF can reduce the adverse reactions of DMF and the stimulate to the stomach. The DMF sustained-release preparation can reduce the number of times drugs have to be administered and improve the patients` compliance.Core beads were prepared by centrifugal granulation. The formulation and process were developed based on single-factor test, the optimized formulation were obtained by an orthogonal test: rotation speed was 12 Hz, feed speed was 15-50 r.min-1, atomized pressure was 1.2 bar, polishing time was 8 min, recovery was 90%. Rotation speed was the most important effect to the recovery of the core beads. Compared with other methods,the method has the advantages of the beautiful appearance, high roundness, particle size distribution, suitable hardness, higher recovery.Using the APAP as the model drug and core beads as nucleus, The fluidized-bed spray process or was adopted for liquid-layering of medicated pellets. The formulation and process were developed based on Orthogonal experiment, the quality of objective pellets was quanlified. The EC was adopted as coating material for coating. The formulation and process of alcohol solvent coating were developed based on single-factor test, the optimized process were obtained by a central composite design; The formulation and process of water-soluble coating were developed based on single-factor test, the optimized process were obtained by a central composite design。 The formulation and process of ethylcellulose aqueous dispersion was rational easy to control. This test had an instructive significance in the preparation of DMF sustained-release pellets of the latter in this paper.The pre-prescription study of DMF showed that: the DMF was stabilizing in water and methanol can meet the demand of experiment in vitro. An HPLC method was set to assay the content as well as to determine the release of DMF in sustained-release pellets. This method is easy to operate with fast speed, the result is accurate with high reliable and high repeatability. This method can be used for the analysis and control of DMF in vitro quality.Medicated pellets were prepared by liquid-layering. The fluid-bed spray process or was adopted for coating of the medicated pellets with Eudragit L30D-55 as sustained-release coating material. The formulation and process of Eudragit L30D-55 coating were optimized by central composition design. The optimized formulation was that : the concentration of coating fluid was 5%,weight of the coating was 4%, the amount of antiadherent was 87.4%, the amount of antistatic agent was 2%; the optimized process was that: the inventory was 130 g, the blast pressure was 0.25 bar, the speed of fluid was 4r/min, the spray pressure was 0.218 bar, the air temperature was 33.3℃.The appearance of DMF sustained-release pellets was smooth, the content was homogeneous, the pellets had a significant sustained release effect in vitro.The preliminary stability showed that: the sustained-release pellets of DMF were sable when exposed to light, but not temperature and high moisture,so it was necessary to be dampproof and high temperature in transportation and storage.The result indicated that:the DMF sustained-release pellets had reliable and stable quality and good release character, which had achieved the forecast aim.