Process Systems Engineering for Pharmaceutical Manufacturing by Ravendra Singh Zhihong Yuan & Zhihong Yuan

Author:Ravendra Singh,Zhihong Yuan & Zhihong Yuan
Language: eng
Format: epub
ISBN: 9780444639660
Publisher: Elsevier Ltd.
Published: 2018-03-15T16:00:00+00:00

Fig. 1 Flexible continuous pharmaceutical tablet manufacturing process. (1) via Direct Compaction (DC), (2) via Dry Granulation (Roller Compaction (RC)), (3) via Wet Granulation (WG).

A continuous direct compaction tablet manufacturing process is the simplest route. There are three gravimetric feeders—with the capability of adding more—that feed the various formulation components (active pharmaceutical ingredient (API), excipient, etc.). A comill is also integrated after the feeder hopper primarily for delumping the powders and creating contact between components. The comill eliminates any large, soft lumps within the powder. The lubricant feeder is added after the comill to prevent overlubrication of the formulation in the comill. These feed streams are then connected to a continuous blender within which a homogeneous powder mixture of all the ingredients is generated. Subsequently, the outlet from the blender is fed to the tablet press via a rotary feed frame. The powder blend fills a die and is subsequently compressed to create a tablet. After compaction, the tablets are coated. Few of the tablets are then sampled for offline measurement of dissolution and other critical quality attributes (CQAs). The NIR sensor for inline monitoring of blend uniformity, blend composition, and blend density has been integrated through a chute placed in between tablet press and blender. Details of the process dynamics of the direct compaction line have been previously reported, and the open-loop as well as closed-loop operation has been extensively studied (Singh et al., 2012, 2013a,b, 2014a,b; Boukouvala et al., 2012, 2013; Vanarase et al., 2010, 2011; Portillo et al., 2010).

The continuous manufacturing process via roller compaction (RC) is called dry granulation route. It is a preferred route for liquid sensitive formulation where wet granulation option is not feasible to use. The roller compaction route also starts with feeders, comill, and blender similar to the DC route. The blender outlet goes to a hopper to keep a consistent level of the powder blend. After blender, the blend goes to a roller compactor. The roller compactor converts the powder blend into ribbon. A mill is integrated with the roller compactor that breaks the ribbon and forms granules. The granules then flow to the tablet press through a transfer pipe (Chute).

In the wet granulation route, the granules are first manufactured and then compacted to form tablets (Singh et al., 2014c). The feeding, comilling, and blending operations are the same as DC route. The outlet from the blender is fed to a hopper to maintain a certain amount of the material holdup to flow into the wet granulator. A twin-screw granulator (TSG) is used to granulate the primary powder. The continuous TSG has three different zones. The feed powder is introduced in premixing zone. The liquid binder is added to the granulator in the next axial zone. Finally, in the wet massing zone, the granules are formed. The granules obtained from the TSG are then sent to a dryer to achieve the desired moisture level. The dry granules can be passed through a mill to break the lumps or oversized granules formed during the granulation process.

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