Direct compression tablet production requires strategies to manage raw material variability, thereby ensuring consistent processing and product quality. Problems related to raw material variability are often only encountered following development, during routine production. At this point, formulation modification is undesirable due to regulatory complexity and related costs. Percolation threshold model is a statistical model that has been identified to analyse and control raw material variability and its effect on tableting process during development. The model outputs a range concentration where the formulation would present poor properties and therefore the ideal drug concentration for robust tablet production and performance.
Percolation threshold (ρ_c) is mathematically given by X=〖S^* (ρ-ρ_c)〗^q, the equation describes the behaviour of a property X when the relative density (ρ) varies. The coefficient q is dependent on the blend. The aim of this study was to model ρ_c for a blend of Ibuprofen and microcrystalline cellulose (MCC) in order to define the critical concentration where the tensile strength decreases. As the coefficient q had not been previously determined for Ibuprofen/MCC blends it was modelled based on a modified Heckel equation. The value calculated was q=3.5 which agrees with other already published empirical values for similar blends. Two MCC grades with differing physical properties were analysed: VivapurŽ 102 (air stream dried quality), and EmcocelŽ 90 (spray dried quality) in order to study the effects of the excipient variability. The threshold values determined were 22.7% and 17.3% w/w Ibuprofen in VivapurŽ and EmcocelŽ, respectively. At Ibuprofen concentrations below these values, the tensile strength was higher, predominated by the excipient network of particles.