Direct compression of cushion-layered ethyl cellulose-coated extended release pellets into rapidly disintegrating tablets without changes in the release profile

Abstract

The aim of this study was to develop and optimize a segregation-free ethyl cellulose-coated extended release multiparticulate formulation to be compressed into tablets without affecting the drug release. Standard tableting excipients (e.g., microcrystalline cellulose, lactose or sorbitol) were layered onto ethyl cellulose-coated propranolol hydrochloride pellets to form a cushion layer in order to eliminate segregation problems normally resulting from particle size difference between coated pellets and excipient powders and second to protect the integrity of the brittle ethyl cellulose coating during compression. The disintegration behavior of the tablets depended strongly on the composition of the cushion layer. Rapid tablet disintegration was obtained with microcrystalline cellulose and the disintegrant sodium croscarmellose. However, the drug release from these cushion-layered pellets still increased upon compression. Incorporation of a glidant into the cushion layer or between the cushion layer and the ethyl cellulose coating reduced the compression effect on drug release markedly. Glidant-containing formulations showed a delayed deformation and damage of the ethyl cellulose-coated pellet upon mechanical stress. In summary, cushion layer based on microcrystalline cellulose facilitated segregation-free compression of a highly compression-sensitive extended release ethyl cellulose-coated pellets into fast-disintegrating and hard tablets without compromising the release properties of the multiparticulates. Directly compressible cushion-layered pellets protected the pellet coating significantly better from damages during tabletting when compared to the conventional compression of blends of coated pellets and excipient powders.