Effect of drying technique and disintegrant on physical properties and drug release behavior of microcrystalline cellulose-based pellets prepared by extrusion/spheronization

The aim of this study was to investigate the influence of drying technique and disintegrant on physical properties and drug release behavior of microcrystalline cellulose-based pellets prepared by extrusion/spheronization. Formulations of paracetamol (6.7%, w/w), microcrystalline cellulose (66.7%, w/w) and different disintegrants, alginic acid, calcium carbonate, d-mannitol, croscarmellose sodium, sodium starch glycolate, crospovidone, in concentrations of 10% or 20% (w/w) were made and processed to pellets by extrusion/spheronization. Different drying techniques, i.e. hot-air drying, microwave drying and freeze-drying, were applied to each formulation. Physical properties, such as particle size distribution, moisture content, apparent density, pellet morphology, were evaluated. The mechanical properties and drug release behavior of the pellets were also examined. Only small difference in crushing strength between hot-air dried and microwave-dried pellets were found. Freeze-drying process resulted in pellets with larger diameter, weaker and more porous than pellets dried with the other processes. The porous structure promoted a faster drug release while the drug release from hot-air dried pellets and microwave-dried pellets was insignificantly different. Different disintegrants were incorporated in the pellets but none of the pellets disintegrated within 90 min. However, the drug release from pellets containing disintegrant was faster than that of pellets with no disintegrant. The results suggested that the type and amount of disintegrant is less influenced than the drying technique.