Abstract

In a recent study, it was demonstrated that improving flow of a model poorly flowing and poorly compactable drug substance, acetaminophen, via dry-coating while using fine excipients may promote direct compression. To validate this novel strategy, particularly for high drug loading formulations, this study investigates the effect of microcrystalline cellulose (MCC) particle size and dry-coating on powder tabletability and flowability. It was determined that blends containing fine-sized MCC (20 μm) resulted in the highest tablet tensile strength and best tabletability since it provides higher inter-particle contact area compared to coarser-sized MCC. While tabletability can be improved by using fine MCC, flowability is poor but can be improved via dry-coating, a process which coats glidants (nano-sized silica) onto particle surfaces. In order to retain the tabletability, which was adversely impacted dues to the presence of glidant in the blend, while simultaneously enhancing flowability via dry-coating, separately blending the drug substance with glidant is shown to be the best method of processing. The combined use of fine excipients and selective dry-coating offers a novel and advantageous formulation strategy in comparison to the conventional use of coarse excipients such as Avicel PH 102 that have been designed and marketed for direct compression.

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