Effect of excipient properties and blend ratio on the compression properties of dry granulated particles prepared from microcrystalline cellulose and lactose

Abstract

In this study, the effect of a systematically varied excipient ratio of a plastic and a brittle material, i.e., microcrystalline cellulose (MCC) and crystalline α-lactose monohydrate (LAC), on the compression properties of dry granulated particles was investigated. Five powders with different MCC:LAC ratios were prepared by dry mixing; subsequently, they were formed into slugs that were milled and sieved, giving granules of two size fractions. Two slugging pressures were used, giving granules of different porosity for each powder. Original powders and granules were compressed, and strain-pressure profiles determined. From these profiles, a series of compression parameters were derived using the Heckel, Kawakita, and Adams compression equations.The initial part of the compression profiles of all granulated powders were similar up to a jamming point, after which the compression profiles diverged depending on the granule composition and the slugging pressure. Parameters derived from the Adams and Kawakita equations reflected the differences in compression behavior, while the Heckel parameter did not. The macroscopic compression stiffening was assessed by the Adams friction parameter which seemed to be controlled by the inner friction of the granules, i.e., their plastic deformation due to inter-particulate flow. The total compressibility, assessed by the Kawakita parameter, was dependent on the initial bulk porosity of the granulations.It is concluded that the composition, microstructure, and packing density of the granules dictated their compression properties, while the granule size and work hardening of primary particles were insignificant.