The relationship between the particle properties, mechanical behavior, and surface roughness of some pharmaceutical excipient compacts

Abstract

Several common pharmaceutical excipient powders were compacted at a constant solid fraction (SF) in order to study the relationship between powder properties, compact surface roughness, and compact mechanical properties such as hardness, elasticity, and brittleness. The materials used in this study included microcrystalline cellulose (MCC), fumaric acid, mannitol, lactose monohydrate, spray dried lactose, sucrose, and dibasic calcium phosphate dihydrate. A slow consolidation process was used to make compacts at a SF of 0.85 (typical for most pharmaceutical tablets) from single excipient components. A model was proposed to describe the surface roughness of compacts based on the brittle or ductile deformation tendencies of the powder materials. The roughness profile would also be dependent upon the magnitude of the compression stress in relation to the yield stress (onset of irreversible deformation) values of the excipients. It was hypothesized that brittle materials would produce smooth compacts with high surface variability due to particle fracture, and the converse would apply for ductile materials. Compact surfaces should be smoother if the materials were compressed above their yield pressure values. Non-contact optical profilometry was used along with scanning electron microscopy to quantify and characterize the surface morphology of the excipient compacts. The roughness parameters R a (average roughness), R q (RMS roughness), R q/ R a (ratio describing surface variability), and R sk (skewness) were found to correlate with the deformation properties of the excipients. Brittle materials such as lactose, sucrose, and calcium phosphate produced compacts with low values of R a and R q, high variability, and negative R sk. The opposite was found with plastic materials such as MCC, mannitol, and fumaric acid. The highly negative skewness values for brittle material compacts may indicate their propensity to be vulnerable to cracks or surface defects. These findings supported the model descriptions and hypotheses. The initial average particle size of the excipients did not directly correlate with compact roughness, probably due to particle deformation during compression. Average roughness values ranged between 0.1 and 1.0 μm for the compacted materials studied. The mechanical properties of the compacts, such as indentation hardness, elastic modulus, and brittle fracture index were also correlated with the roughness values. Pertinent correlations were found between average roughness, compact mechanical properties and the excipient type (either brittle or ductile). From this study, it can be concluded that brittle excipient powders generally produced smooth and brittle compacts, and plastic materials produced rough and ductile compacts. Surface roughness was hence found to be a useful descriptive property for pharmaceutical composites and supporting a model based on the excipient powder properties.