(444f) A Novel Continuous Device for Surface Modification of Cohesive Pharmaceutical Powders Via Dry Coating of Nano-Particles for Improved Powder Flow Performance

A new continuous method for applying nano-sized guest particles onto pharmaceutical and other host particles (a.k.a. ?nanocoating? or ?dry-coating?) has been developed based on modification of conventional processing equipment. This new device has been shown to be capable of coating nano-additives onto the API and excipient particle surfaces without significant host particle attrition. Our previous work has already established that surface modification via dry coating achieves adherence of nano-particles onto host particles through strong van der Waals attraction, and the resulting product has significantly reduced bulk powder cohesion, hence improved flow and packing density. This work provides a new, practical and scalable method to potentially achieve these improvements. The newly developed device was used to dry coat several APIs and excipients with nano-silica and other flow promoters. The particle morphology and coating extent (Scanning Electron Microscopy), particle size distribution (laser diffraction), bulk density, and flow performance (shear cell testing) of APIs, coated APIs, excipients, coated excipients and formulated blends were assessed. It was found in all cases that after dry coating, the powders exhibited a significant and in some cases outstanding improvement in flow performance (e.g. flow function coefficient increase from 3 to >10) and in bulk density. This novel coating process was successfully scaled from a laboratory scale to a pilot scale with equivalent positive flow improvements. Formulated drug product blends containing 10 to 60% coated API exhibited superior flow performance relative to equivalent blends with uncoated APIs. The resulting blends also exhibited substantial increase in bulk densities, suggesting potential for elimination of wet granulation and hence simplifying tablet formulations. This particle engineering work describes the first successful demonstration of using a continuous process capable unit operation for uniform nano-coating via dry approach and highlights the substantial improvements to powder flow properties when this approach is used.