A Comprehensive Review of the Rheological Properties of Powders in Pharmaceuticals

Abstract

The perpetual significance of the pharmaceutical industry in society necessitates ongoing research efforts to enhance the efficacy of its manufacturing processes. Given that drug product manufacturing typically involves powder processing, a thorough understanding of powder characterization is needed for optimal process performance. Powder rheology is commonly examined in pharmaceutical manufacturing to elucidate the relationship between powder properties and the performance of pharmaceutical processes. This paper provides a brief discussion of recent literature regarding the various powder properties and characterization techniques encompassed in powder rheology. The powder properties are categorized into particle size, particle morphology, friability, electrostatics, permeability, wettability, cohesion, bulk density, and agglomeration sections. A distinct focus is placed on the segment about powder wettability. This review informs readers about the fundamental properties of powders known to influence pharmaceutical processes. It discusses the interrelationships among these properties, powder characterization techniques, and ideal states of powder properties that lead to optimal process performance.

Introduction

The pharmaceutical industry plays a crucial role in safeguarding the well-being of billions of individuals. Despite its significant impact, the industry faces ongoing challenges, prompting continuous research and improvement efforts. In recent years, there has been a notable shift from traditional batch processing to continuous manufacturing methods, driven by the benefits of enhanced safety and product quality control [1–5]. This transition has garnered considerable attention, but an equally important focus remains on understanding and characterizing powders and granular materials used in pharmaceutical manufacturing.

Powders are integral to various unit operations in pharmaceutical processes. Given that tablets represent upwards of 70% of all marketed drugs, the unit operations used in tablet manufacturing are particularly prevalent [6]. Key unit operations, such as feeders, blenders, and tablet press machines, are essential components of this process [2]. These operations often encounter issues tied to powder behavior, leading to performance challenges [7–11]. Given the centrality of powders in pharmaceutical operations, a precise understanding of their behavior is vital for ensuring optimal product quality [12–16]. Nevertheless, powders remain a complex and inadequately understood subject [17–19]. This knowledge gap has given rise to a significant body of literature dedicated to the quantification and prediction of powder behavior, known as powder rheology. Describing powder flow is uniquely challenging, as it defies rigid adherence to a set of rules or equations. Powders can exhibit solid-like compaction, liquid-like flow, and even gaseous properties during manufacturing processes. Consequently, characterizing powders demands the use of multiple parameters rather than relying on a single metric to assess flow accurately [20–22].

The subsequent sections of this paper provide a comprehensive literature review of powder properties, with a particular emphasis on wettability, and the associated characterization techniques most pertinent to pharmaceutical manufacturing. This review aims to meticulously describe the components of this paper in a way that effectively informs readers about powder rheology due to its paramount importance and various applications.

2. Importance of Powder Flowability in Pharmaceutical Manufacturing

Powder characterization techniques are employed to assess flowability, defined as a powder’s ability to flow under specific conditions [17]. Each technique yields one or more parameters that describe a particular powder property and quantify how a powder behaves in various circumstances. Although these parameters are interrelated [23], their evaluation of flowability often hinges on the stress state of the powder bed [24,25].

This implies that the same powder may yield significantly different results when subjected to testing under motionless or flowing conditions. Therefore, selecting appropriate characterization techniques is vital to prevent conflicting results among parameters. A plethora of parameters are employed in the literature to evaluate powder flowability in pharmaceutical operations, with each parameter associated with properties such as particle size, particle morphology, friability, electrostatics, permeability, wettability, cohesion, bulk density, and agglomeration [26–32].

These properties are typically analyzed through multiple characterization techniques, and the effectiveness of these techniques is often compared in the literature [33–35]. Flowability assessments are commonly coupled with the objective of improving powder flow in pharmaceutical manufacturing. This is frequently achieved through techniques like dry coating, where active pharmaceutical ingredients (APIs) are coated with nanoparticles [36–39]. Other methods include adding lubricants to blend formulations and controlling humidity to manage moisture content and other powder parameters [40–42].

Flowability assessments may also be used in efforts to improve the efficacy of drug delivery methods, such as dry powder inhalation and orodispersible tablets [43–45]. Beyond enhancing flowability, these powder parameters also shed light on the relationship between powder properties and the performance of pharmaceutical manufacturing processes. As mentioned earlier, suboptimal powder behavior can lead to unsatisfactory operational performance in pharmaceutical processes such as tableting and mixing [46–48].

Accurately evaluating powder properties is critical for properly determining and predicting a powder’s flowability. This pursuit also elevates our understanding of the connections between powder flowability and pharmaceutical process performance, as well as the relationships between various powder properties.

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Brubaker, J.; Moghtadernejad, S. A Comprehensive Review of the Rheological Properties of Powders in Pharmaceuticals. Powders 2024, 3, 233–254. https:// doi.org/10.3390/powders3020015

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