Compound Acetaminophen Sustained Release Pellets

This thesis was aiming at the research of compound sustained-release pellets, consisting of preparation methods for pellets, the sustained release system of coated pellets and matrix pellets, stability, pharmacokinetics and pharmacodynamics. Results show: the compound sustained-release pellets had a marked sustained-release property and the drug was sustained released in vitro over 1 2h. First, the formulation and technology of Acetaminophen prompt-release pellets was optimized with orthogonal experiment design. Aqueous dispersion(EudragitNE3OD) was used as coating material, which can be applied in conventional pan coating. The effects of process variables and formulation variables on pellets preparation were investigated. The formulation and technology of Acetaminophen sustained-release coated pellets was optimized. Results show. the coated pellets had a marked sustained- release property, the drug release profiles in vitro followed first order kinetics. The coating level and the amount of poremaking agent can alter the drug release rate. Dextromethorphan hydrobromide sustained-release matrix pellets were produced by extrusion-spheronisaion. The effects of process variables and formulation variables on pellets preparation drug release were investigated. The formulation and technology of Dextromethorphan hydrobromide sustained-release matrix pellets was optimized. Result show: it is possible to prepare sustained-release pellets by extrusion-spheronisation with ethyl 2 ABSTRACT cellulose and stearic acid as the matrix materials. The sustained action can be achieved without the need to coat the pellets. The sustained-release matrix pellets haLl a marked sustained-release property, the drug release profiles in vitro followed Hlguchi kinetics. The amount of MCC can alter the drug release rate. The FORTRAN computer program was applied to adjust the proportion of pellets to control drug release rate, the blended pellets meet with requirements. The drug content and release stability of the sustained release capsule were both very good under high temperature tests, high moisture and light test. Pharmacokinetics and bioavailability studies of compound sustained-release capsule and market tablets in dogs were performed based on determination of plasma concentration of drugs at different intervals after a single oral administration. T~ of compound sustained-release capsule was 3 -?-4 hours, of market tablets was 1.5 ? hours. The relative bioavailability of acetamincphen and Dextromethorphan hydrobromide were 99.65% and 97.2% compared with market tablets. It was very significant between the absorption in-vivo and the dissolution in-vitro. Consequently, compound sustained- release capsule dosed twice a day is expected to show a more efficiency than its market tablets dosed 3 棏4 times a day.