The Influence of Equipment Design and Process Parameters on Granule Breakage in a Semi-Continuous Fluid Bed Dryer after Continuous Twin-Screw Wet Granulation

Abstract

The drying unit of a continuous from-powder-to-tablet manufacturing line based on twin-screw granulation (TSG) is a crucial intermediate process step to achieve the desired tablet quality. Understanding the size reduction of pharmaceutical granules before, during, and after the fluid bed drying process is, however, still lacking. A first major goal was to investigate the breakage and attrition phenomena during transport of wet and dry granules, the filling phase, and drying phase on a ConsiGma-25 system (C25). Pneumatic transport of the wet granules after TSG towards the dryer induced extensive breakage, whereas the turbulent filling and drying phase of the drying cells caused rather moderate breakage and attrition. Subsequently, the dry transfer line was responsible for additional extensive breakage and attrition. The second major goal was to compare the influence of drying air temperature and drying time on granule size and moisture content for granules processed with a commercial-scale ConsiGma-25 system and with the R&D-scale ConsiGma-1 (C1) system. Generally, the granule quality obtained after drying with C1 was not predictive for the C25, making it challenging during process development with the C1 to obtain representative granules for the C25.

Continuous Twin Screw Granulation: A Review of Recent Progress and Opportunities in Formulation and Equipment Design

“…The most commonly used immediate release binders in twin screw wet granulation of drug-loaded formulations are cellulose derivatives such as hydroxypropylmethylcellulose (HPMC) [ 12 , 21 , 57 , 66 ] and hydroxypropylcellulose (HPC) [ 26 , 29 , 67 , 68 , 78 , 79 ] as well as synthetic polymers such as polyvinylpyrrolidone (PVP) [ 14 , 25 , 59 ]. Although cellulosic binders are also commonly used in batch manufacturing, they are not always the most suitable choice for twin screw granulation.…”

“…Consequently, the assessment of an optimized screw configuration often remains rather empirical, although the impact of screw configuration on granule characteristics and processability is widely recognized. Generally, powder is added on top of a long conveying section that transports the blend towards one or two kneading blocks, consisting of multiple kneading elements positioned at a certain offset or stagger angle (mostly 60° forward) [ 21 , 46 , 54 , 57 , 94 , 102 ]. Towards the end of the granulation screws, often size control/chopping/screw mixing elements are implemented to reduce the oversized fraction and obtain a more monomodal PSD [ 2 , 52 , 68 , 83 ].…”

“…Furthermore, raw materials are not subjected to moisture or heat, which reduces the risk of degradation. However, this pathway requires the blend to have favorable flowability and compaction properties as well as high content uniformity [ 18 , 19 , 20 , 21 ]. To overcome these requirements, intermediate granulation steps (mostly wet and dry granulation) can be implemented.…”

Blend Segregation in Tablets Manufacturing and Its Effect on Drug Content Uniformity—A Review

“…For instance, a developmental API has been found to undergo bulk fragmentation and a size reduction during the feeding in a horizontal screw feeder even though it resisted comminution in a tumbling blender and conical mill [43,44] Other reports have described the granules' attrition in continuous twin screw granulation lines, namely during the transfer of wet granules to the fluid bed dryer and at the transfer line of dried granules. The effect of a diminished 'oversized' fraction and an increased fine content was more pronounced for pneumatic conveyance lines than for gravitational transfer, and the susceptibility of the dry material to breakage was related to formulation composition and final moisture content, so that the drying process needed to be optimized for the generation of sufficiently solid bonds for the material to resist comminution [45,46]. However, the aforementioned papers did not assess any segregation events relating to the attrition.…”

Advances in Twin-Screw Granulation

“…TSG found its roots in the late 1990s, evolved rapidly in the last decade as a promising wet granulation technology and was commercialized by some of the leading equipment manufacturers, such as GEA and ThermoFisher. Drying is the obvious downstream step of twin-screw wet granulation and is achieved mainly by a semi-continuous fluid-bed dryer [1]. While the early applications of TSG were focused on the wet granulation process, it is now gaining ground as an alternative dry granulation method, namely melt granulation [2].…”