Understanding pellet-filler interactions in compression of coated pellets

Abstract

There is a strong interest to compress coated multiparticulates into tablets. In order to preserve the coat function during compression, it is important to understand the pellet-filler interactions. Hence, the influence of the physical properties of fillers, compression pressure as well as the pellet type and size, on coat damage was investigated. Interestingly, depending on the filler material, the extent of coat damage either increased linearly or had no direct relationship with the filler particle size. Among the different fillers investigated, the extent of pellet coat damage due to compression was lowest with micronized lactose. In addition, when added as an adjuvant filler, micronized lactose also reduced the extent of pellet coat damage caused by the coarser grades of lactose. Irrespective of the filler type, coated pellets were found to undergo three phases of coat damage with two transition points over a range of compression pressure. There was minimal coat damage at the initial particle rearrangement phase. This was followed by an attritive phase where the extent of coat damage escalated beyond the first critical transition point. The drug dissolution rate was observed to decrease slightly in the third phase.