The comparison of conventional surface metrology and area-scale fractal parameters to differentiate the surface topography of pharmaceutical excipient compacts and preliminary investigation of scale-based correlations with excipient properties were performed. The determination and selection of the most appropriate surface topography parameters is important in optimizing the design and quality of industrial processes and products. The surfaces of three types of excipient compacts (microcrystalline cellulose (MCC), spray dried lactose (SDL), and dibasic calcium phosphate dihydrate (DCPD)) were characterized with a non-contact optical surface profilometer. A statistical F-test matrix was used to rank and quantify the ability of conventional surface texture parameters: Sa, Sq, St, Ssk, Sku, and the fractal parameters: relative area, Asfc (complexity) and SRC (smooth–rough crossover), to differentiate the surfaces of the compacts. Based on this statistical analysis and area-scale plots generated from profilometer data, it was found that most of the conventional parameters were suitable for distinguishing the surfaces. The F-test applied to the relative areas as a function of scale also indicated the ranges of scales over which the differentiation was possible. MCC–SDL and DCPD–SDL material pairs were able to be differentiated between scales of 10 and 10,000 μm 2, however, MCC–DCPD pairs were only differentiable between 300 and 2000 μm 2. A new method was established for illustrating the scale-based correlations, using the product of the regression coefficient and the normalized slope. The correlations between the fractal parameters and the properties of the excipients, including brittle fracture and indentation hardness, gave plausible explanations for the similarities between certain excipients, supporting a phenomenological understanding of the behavior of excipient compacts and their surfaces.
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