(440d) Coating Device Performance on Dry Coating Effectiveness: Accounting for Device Intensity on Silica Dispersion and Agglomeration

Fine powders in pharmaceutical manufacturing are inherently cohesive, leading to significant processing challenges, including poor flowability, inconsistent blending, bridging in hoppers, and unreliable tablet compression[1-6]. Mitigating cohesion through nano dry particle coating has emerged as a practical solution, where nanoscale guest particles (typically silica) modify the surface properties of larger host particles[7-12]. Contact mechanics primarily govern the mechanism underlying the working principle of dry coating based on van der Waals forces, wherein artificial surface roughness reduces inter-particle adhesion by creating [7, 13, 14] a critical balance exists in the separation caused by nanoparticle coating, leading to minimum cohesion reduction, hence explains why achieving a uniform monolayer coating of nanomaterials on the host surface is highly desirable[13]. Non-uniform coating or silica agglomeration may compromise this expected cohesion reduction, limiting the effectiveness of the dry coating process.

Various factors influence dry coating quality, including silica concentration, host-guest compatibility, material properties like elasticity, hardness, and host material surface morphology[10, 12, 15-17]. However, the most critical factor is processing shear intensity, which determines the ability to break guest agglomerates and achieve uniform dispersion on host particles[16]. This study systematically evaluates three industrially relevant devices with varying shear intensities—V-blender (low-intensity batch), comil (medium-intensity continuous), and LabRAM (very high-intensity batch)—for their effectiveness in reducing cohesion and improving the bulk properties of pharmaceutical materials through silica dry coating. Three very cohesive and cohesive model test materials, i.e., micronized acetaminophen (mAPAP), coarse acetaminophen (cAPAP), and griseofulvin (GF), are tested for property improvement comparison. Two silica types (A200 and R972P) were investigated at 100% surface area coverage. Results demonstrated that processing intensity significantly impacts coating effectiveness and powder bulk property improvements. The V-blender showed only marginal improvements in flow properties that plateaued across all processing times. Even after extended processing, SEM images revealed poor silica dispersion and highly porous aggregates. Comil results in better performance than Vblender and could also be optimized. Its performance improved with decreasing sieve size and adopting a multiple-pass approach which facilitates higher “residence time”. However, some silica agglomeration remained visible even at the highest shear levels. LabRAM achieved the most significant property improvements, with 2-3 regime enhancements in FFC and CBD at higher intensity (70-90Gs), creating well-dispersed discrete silica coating, with some spherical agglomerates of very low porous structure.

A multi-asperity model[7] explaining the relationship between silica dispersion characteristics and adhesion forces was further refined to account for property improvements observed under different processing conditions, while also considering silica agglomeration. The model correlates the effect of silica agglomerate morphology to coating effectiveness, demonstrating how fractal dimensions affect the equivalent agglomerate diameter and porosity for the same number of silica particles. Lower intensity resulted in elongated, highly porous agglomerates (lower fractal dimension), while higher intensity processes resulted in more spherical, compact agglomerates (higher fractal dimension) that more effectively reduced inter-particle adhesion.

This work establishes performance equivalence criteria between different dry coating devices and provides guidelines for translating processing conditions across equipment scales. It addresses critical gaps in pharmaceutical formulation development and scale-up processes for dry particle coating, while providing mechanistic insights into cohesion reduction mechanisms via dry coating.

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