Study of diminutive granules as feed powders for manufacturability of high drug load minitablets.

The maximal amount of drug contained in a minitablet is limited. To reduce the total number of minitablets in a single dose, high drug load minitablets can be prepared from high drug load feed powders by various pharmaceutical processing techniques. Few researchers have however examined the influence of pharmaceutical processing techniques on the properties of high drug load feed powders, and consequently the manufacturability of high drug load minitablets. In this study, silicification of the high drug load physical mix feed powders alone did not yield satisfactory quality attributes and compaction parameters to produce good quality minitablets. The abrasive nature of fumed silica increased ejection force and damage to the compaction tools. Granulation of fine paracetamol powder was crucial for the preparation of good quality high drug load minitablets. The diminutive granules had superior powder packing and flow properties for homogenous and consistent filling of the small die cavities when preparing minitablets. Compared to the physical mix feed powders for direct compression, the granules which possessed higher plasticity, lower rearrangement and elastic energies, yielded better quality minitablets with high tensile strength and rapid disintegration time. High shear granulation demonstrated greater process robustness than fluid bed granulation, with less discernment on the quality attributes of feed powder. It could proceed without fumed silica, with the high shear forces reducing interparticulate cohesivity. An in-depth understanding on the properties of high drug load feed powders with inherently poor compactability and poor flowability is important for the manufacturability of high drug load minitablets.