Charge reduction assisted production of diminutive fluid bed granules for high drug load minitablets.

Micronized drug powders are generally unsuitable as tableting feed to produce minitablets due to their cohesivity and poor flow. The silicification of fine paracetamol powder (PCM) with an optimal concentration range of fumed silica (fSi) [0.7-0.9%, w/w] reduced the net negative charge of PCM and improved powder flow. The optimal fSi concentration range suitable was established through the measurement of charge and flowability of the silicified powders. Silicification of PCM by physical mix did not satisfactorily overcome the cohesive forces between the PCM crystals and improve powder flow sufficiently such that it will feed consistently into the smaller die orifices during tableting. Using a specialized fluid bed system with swirling air and side spray, controlled granulation of silicified PCM packed and agglomerated the interlocking-prone needle shaped PCM crystals into diminutive granules that are more spherical and free flowing. With optimized fSi concentration (≈ 0.8%, w/w) and granulation process parameters, high drug load diminutive granules (D≃ 90 μm) were successfully prepared from PCM as starter seeds (D≃ 30 μm). Minitablets prepared from the diminutive granules had low weight variation, and were mechanically strong with disintegration time of <30 s. This study demonstrated the feasibility of producing high drug load minitablets from a cohesive, electrostatic-prone fine drug powder.