Tablets & Capsules

TC0719

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Tablets & Capsules July 2019 33 C In batch manufacture of a tablet formulation, you pro- cess predetermined quantities of API and excipients together in a single unit operation, which you complete in its entirety before passing to the next unit operation. You have a predetermined batch size and theoretical yield. Some of your unit operations may be inherently continuous, such as sieving, milling, and tablet compres- sion, but you typically carry out blending and wet-granu- lation on the entire batch at once. In continuous manu- facturing at a quasi-steady state, all unit operations are occurring simultaneously. As you continuously feed the API and excipients into the equipment train, you produce tablets and remove them from it. Each type of processing has advantages and disadvan- tages. For example, if some catastrophic failure occurs in batch processing, you may lose the whole product batch, while in continuous manufacturing, a catastrophic failure may cause you to lose only part of the batch [1]. In truly continuous operations, operator intervention isn't possi- ble if you need to accommodate variations in component properties, such as end-point detection in wet granulation or dry blending. If the process requires an intervention, you must consider some form of hybrid approach, in which you run a particular unit operation in batch mode and then convert the process train back to continuous mode again. An even better option would be to engineer the variability out of the formulation and/or process. Another advantage of continuous manufacturing is that it allows for real-time release testing (RTRT), when combined with an appropriate set of PAT sensors and controls, which saves on costly post-process testing. Constraints on adoption of continuous manufacturing Again, in truly continuous manufacturing operations, the opportunity for operator intervention and/or process- ing to an end point is nonexistent unless you implement such controls using a hybrid approach, which isn't opti- mal. Continuous manufacturing requires you to resolve other issues as well, including: • Determining how to meter low-dose and very- fine materials, including highly potent APIs (HPAPIs) and excipients present at low levels in the formulation, such as lubricants, glidants, and possibly disintegrants. This article discusses the role of excipients in the pharmaceuti- cal industry's adoption of continuous manufacturing and describes ways in which stakeholders can facilitate the transi- tion to continuous processes. ontinuous manufacturing of pharmaceutical finished products is now a reality. At this time, pharmaceutical companies are using continuous processes to manufacture four drug products licensed in the US and Europe. They are all solid oral dosage forms (SODFs). One drug prod- uct was a conversion from a batch process; the other three used continuous methods from the outset. In principle, you can apply continuous manufacturing to most types of pharmaceutical dosage forms, but you have to make a product in sufficient volume to justify the investment. It isn't surprising that most interest lies in SODFs, because they are the most common formulation types and are typically manufactured in large quantities. Continuous manufacturing is a logical extrapolation from the combination of process analytical technology (PAT) and quality-by-design (QbD) in pharmaceutical development and manufacturing. Certainly, it's difficult to imagine achieving the successful development of a continuously manufactured tablet or capsule without the enhanced understanding required under QbD and the enhanced monitoring capabilities from the proper imple- mentation of the necessary PATs. Continuous manufacturing imposes different con- straints on available excipients compared to conventional batch manufacturing and requires a better understanding of why the excipients work and what is important for their functionality and performance. This article attempts to provide some indications of the types of understanding that may be important. Batch versus continuous manufacturing The logical first step is to consider the differences between batch and continuous SODF manufacturing. For example, consider an immediate-release tablet formula- tion. (Similar considerations would apply to immedi- ate-release powder-filled hard capsules.) Excipients and continuous manufacturing Chris Moreton FinnBrit Consulting continuous manufacturing

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