This study aimed to develop novel co-processed tablet fillers based on the principle of particle engineering for direct compaction and to compare the characteristics of co-processed products obtained by fluid-bed coating and co-spray drying, respectively. Water-soluble mannitol and water-insoluble calcium carbonate were selected as representative fillers for this study. Hydroxypropyl methylcellulose (HPMC), serving as a surface property modifier, was distributed on the surface of primary filler particles via the two co-processing methods. Both fundamental and functional properties of the products were comparatively investigated. The results showed that functional properties of the fillers, like flowability, compactibility, and drug-loading capacity, were effectively improved by both co-processing methods. However, fluid-bed coating showed greater advantages over co-spray drying in some aspects, which was mainly attributed to the remarkable differences in some fundamental properties of co-processed powders, like particle size, surface topology, and particle structure. For example, the more irregular surface and porous structure induced by fluid-bed coating could contribute to better compaction properties and lower lubricant sensitivity due to the increasing contact area and mechanical interlocking between particles under pressure. More effective surface distribution of HPMC during fluid-bed coating was also a contributor. In addition, such a porous agglomerate structure could also reduce the separation of drug and excipients after mixing, resulting in the improvement in drug loading capacity and tablet uniformity. In summary, fluid-bed coating appears to be more promising for co-processing than spray drying in some aspects, and co-processed excipients produced by it have a great prospect for further investigations and development.
Novel binary co-processed fillers comprising a plastic material (HPMC) and a partially brittle material (mannitol or calcium carbonate) were developed via fluid-bed coating and spray drying in this study. The surface modification of primary filler particles with HPMC effectively solved their poor flowability and compactibility, hence making them more suitable for direct compaction. The comparison of the two co-processing methods indicated that some features introduced by fluid-bed coating could not be achieved by spray drying. Although both methods improved the direct compaction performances of powders, fluid-bed coating showed greater potential in some aspects, including compactibility, lubrication sensitivity, and drug-loading capacity. This was believed to be mainly due to the special particle structures (porous large agglomerates with irregular surface) formed by fluid-bed coating, which couldincrease contact area and mechanical interlocking 563 between particles under pressure. In addition, more effective surface distribution of HPMC during fluid-bed coating should also be a contributor. As a whole, co-processed excipients produced through the fluid-bed coating method are more promising and worthy of further Exploration.