In vitro behavior of dronedarone hydrochloride loaded pellets using vacuum impregnation technique

Pharmaceutical pellets are a versatile and adaptable drug carrier system with pharmacological and technological advantages specific to multiparticulate delivery systems. Depending on their porosity and formulation procedure, a controlled drug release pattern can be achieved using a variety of pellet production and drug loading techniques. In the present paper, we have developed microcrystalline cellulose based porous pellets by extrusion/spheronization process. Two types of dronedarone hydrochloride suspensions were prepared in order to load drug onto carrier pellets using vacuum impregnation method. Despite its extensive use in the biomedical field of research, this technique hasn't been applied yet as means of incorporating drugs into inert and porous pellets. In addition, drug release control was tested by spray coating the pellets with hydroxypropyl methylcellulose in a fluidized bed. Pellet morphology, porosity and dissolution behavior were determined and the results indicate that DNR particle size affects the drug incorporation mechanism and, therefore, drug release patterns obtained through in vitro tests. Additionally, it was proven that polymer-based film-coat significantly slows down the drug release from the pellets. In vitro studies of the coated pellets in biorelevant fluids have shown that DNR release profiles are directly related to the type of dissolution media used. Vacuum impregnation was found to be promising technique for incorporation of DNR onto the surface of the porous pellets and into their pores.