Heather Emady

Analysis of the origins of content non-uniformity in high-shear wet granulation

In this study, the origins of granule content non-uniformity in the high-shear wet granulation of a model two-component pharmaceutical blend were investigated. Using acetaminophen as the active pharmaceutical ingredient (API) and microcrystalline cellulose as the excipient, the distribution of the API across the granule size classes was measured for a range of conditions that differed in the duration of the initial dry mixing stage, the overall composition of the blend and the wet massing time. The coarse granule fractions were found to be systematically sub-potent, while the fines were enriched in the API. The extent of content non-uniformity was found to be dependent on two factors - powder segregation during dry mixing and redistribution of the API between the granule size fractions during the wet massing phase. The latter was demonstrated in an experiment where the excipient was pre-granulated, the API was added later and wet massed. The content non-uniformity in this case was comparable to that obtained when both components were present in the granulator from the beginning. With increasing wet massing time, the extent of content non-uniformity decreased, indicating that longer wet massing times might be a solution for systems with a natural tendency for component segregation.

Granulation and Tabletting

This chapter provides an overview of the granulation and tabletting processes, with a focus on wet granulation. The emphasis is on the applications of wet granulation, including practical advice for the design, operation, and control of the equipment, as well as specific industrial applications. Although the mechanisms are fairly well understood, achieving better product control remains a challenge, and therefore is an active area of research.

Granule formation and structure from single drop impact on heterogeneous powder beds

ABSTRACT Single drop impact of liquid on a static powder bed was studied to investigate the granule formation mechanism, droplet penetration time, as well as the characterization of granules (morphology, surface structure and internal structure). Water was used as the liquid and two pharmaceutical powders, microcrystalline cellulose (MCC) and acetaminophen (APAP), were mixed to make heterogeneous powder beds. The complete drop impact and penetration was recorded by a high speed camera. Two granule formation mechanisms that have been identified previously occurred: Spreading and Tunneling. Spreading occurred for mixtures with an APAP amount of less than 20%, while Tunneling started to occur when the APAP amount increased above 20%. With an increase of APAP concentration, the mean particle size decreased, drop penetration time increased, and the granules formed became smaller in size, which was in good agreement with previous literature. The granule morphology, surface structure, and internal structure were characterized by a prism method with image analysis, scanning electron microscopy (SEM), and X‐ray microtomography, respectively. The Spreading mechanism produced flat disks with a porous internal structure, while the Tunneling mechanism produced round granules with a dense internal structure. There is a clear trend of decreasing porosity and increasing roundness of granules made from heterogeneous mixtures within the transition from Spreading to Tunneling. It is believed that the mean particle size of the powder bed and the powder‐liquid contact angle are the predominant factors in influencing the formation mechanism, drop penetration time, and granule properties.