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32 May 2020 Tablets & Capsules eye on excipients Manufacturers favor continuous direct compression of tablet for mulations because it is economical and efficient, but the process presents a variety of manu- facturing challenges related to content uniformity, compactibility, and flow. This edition of "Eye on Excipients" explores a method for incorporating a co-processed excipient into a tablet for- mulation to facilitate direct compression tableting and create more robust tablets. Although traditional batch pro- cessing has long been the norm in the pharmaceutical industry, drug product manufacturers have begun to shift toward continuous manufac- turing as a more sustainable, eco- nomical, and time-efficient method. Key benefits of continuous manu- facturing include better process con- trol, simpler scale-up or none at all, enhanced safety margins, increased productivity, and improved quality and yields. In addition, the equip- ment needed for continuous man- ufacturing is much smaller than its batch counterpart, and it operates at a steady state, which facilitates auto- mation and process monitoring. Tablets are the most common dosage form, comprising around 70 percent of the global oral drug deliv- ery market [1]. As a result, many for- mulators transitioning to continuous operations have led with direct com- pression (DC) tableting. Continuous DC tableting allows for the ingredi- ents to be processed and compressed seamlessly without a granulation step, making it more economical than tra- ditional batch tableting. While direct compression of a formulation improves efficiency, the lack of an intermediate granulation step can present a challenge because most pharmaceutical ingredients do not have inherent binding proper- ties. High-dose tablets may lack suf- ficient tensile strength if the active pharmaceutical ingredient (API) is not easily compressible, while low- dose formulations may be difficult to blend uniformly. Additionally, since some APIs are hygroscopic and thermolabile (heat sensitive) in nature, they can be difficult to com- press. Excipients, such as diluents, fillers, and binders can play a signif- icant role in improving a formula- tion's content uniformity, flow, and compaction properties as well as the resulting tablet's tensile strength. Incorporating co-processed excipients One of the keys to overcoming these challenges is to select excip- ients that both integrate well with the formulation and offer suitable powder flow properties, to ensure consistent tablet weight and content uniformity. Choosing the correct excipient can also help manufacturers avoid ingredient segregation during the blending process, improve flow and transfer to the equipment train, and achieve proper lubrication for one-step mixing. Co-processed excipients, which are a combination of two to three excipients developed via co-process- ing, may be the answer. They offer functionalities exceeding those of traditional physical excipient blends, allowing formulators to reduce man- ufacturing steps while ensuring tablet quality. Co-processed excipients lend themselves well to continuous opera- tions because they are engineered to achieve the synergistic properties of a tableting blend's key components in a single, highly flowable and com- pressible granular material [2]. Formulators whose DC tablet- ing operations are faced with par- ticle segregation, poor API content uniformity, and excipients plugging or blocking the manufacturing pro- cess should seek out an excipient that improves powder flow and tablet compactibility, thus helping to main- tain API uniformity within the tablets. This article describes a study in which researchers, using different grades of a co-processed excipient, examined powder flow, compact- ibility, and tablet tensile strength, during the direct compression pro- cess. For the study, the researchers selected a silicified microcrystalline cellulose (Avicel SMCC, DuPont) that consists of 98 percent w/w microcrystalline cellulose (MCC) and 2 percent w/w silicon dioxide. They chose SMCC because it does not alter the chemical structure of MCC yet exhibits improved compac- tion and powder flow properties. The researchers first examined the flow characterization of the SMCC according to the pharmacopoeial methods [3], and performed a vari- ety of simple and rapid tests, such as Vinay Muley, Fernanda Onofre, Michael Baumann, and Juergen Engelhardt DuPont Nutrition & Biosciences