Study On Propafenone Hydrochloride Sustained Release Pellets

In this paper, sustained release pellets was prepared using propafenone hydrochloride as model drug. The purpose of present study was designed to develop a kind of sustained release pellets which would reduce times of administration and decrease adverse effects, and would be more convenient for patients to use. Ultraviolet spectrophotometry (UV) was utilized to determine the propafenone hydrochloride content in pellets, and assay release of propafenone hydrochloride sustained release pellets. The concentration of propafenone hydrochloride in dogs' plasma was assayed by high-performance liquid chromatography (HPLC).Propafenone hydrochloride pellets were prepared by extrusion-spheronization. The properties of pellets were investigated by yield, particle size distribution, bulk density, surface shape, roundness and friability. Through the formulation screening and process observation, it was showed that the yield of the objective pellets (20/24 mesh cut) was above 70%. The results suggested the extrusion-spheronization technology for propafenone hydrochloride may reach the expected goals.A fluid-bed spray processor was adopted for coating the pellets prepared by extrusion-spheronization. The coating process variables were determined and controlled. A sustained release pellet system was produced by coating with Eudragit^?NE30D, or Eudragit^?RS30D and Eudragit^?RL 30D at a ratio of 1:3, respectively. The factors including a series of plasticizer TEC, talc, static electricity-proofing SDS, coating level and curing time were investigated. Central composite design and orthogonal design were used to optimize the two coating formulations respectively, and the best optimized range were obtained .The description of dissolution profiles suggested that the drug release following the first-order kinetics.The matrix sustained release pellets were also prepared by extrusion-spheronization. Investigation of the content of ethyl cellulose (EC) and stearic acid (SA), the content of microcrystalline cellulose (MCC), the ratios of EC and SA was used to obtained a good formulation. The mechanism of release results from the matrix rode and drug diffusion of matrix by describing the drug release curve fitted Higuchi and Ritger-Peppas model.The results of stability experiments showed that light, temperature and moisture had little effect on sustained release pellets . The plasma concentration in six healthy dogs was tested after a single oral administration of commercial and test formulation. Plasma concentration-time profiles were determined by HPLC. The pharmacokinetics parameters after a single oral administration of commercial and test formulation analyzed by non-compartment model theory were AUC_0～t 8.45±0.84μg·h/mL and 7.88±0.98μg·h/mL, C_max1.41±0.13μg/mL and 1.92±0.05μg/mL, t_max6.0±1.6 h and 1.5±0.5 h, respectively. The relative bioavailability of propafenone hydrochloride sustained release pellets was 96.4±15.0%. Good correlation existed between absorption percent in vivo and dissolution percent in vitro.