Advances in Twin-Screw Granulation

Twin-screw granulation (TSG) is an emerging process technology that allows both wet and dry granulation of powders with a wide range of properties [...]

Advances in Twin-Screw Granulation Processing

Twin-screw granulation (TSG) is a pharmaceutical process that has gained increased interest from the pharmaceutical industry for its potential for the development of oral dosage forms. The technology has evolved rapidly due to the flexibility of the equipment design, the selection of the process variables and the wide range of processed materials. Most importantly, TSG offers the benefits of both batch and continuous manufacturing for pharmaceutical products, accompanied by excellent process control, high product quality which can be achieved through the implementation of Quality by Design (QbD) approaches and the integration of Process Analytical Tools (PAT). Here, we present basic concepts of the various twin-screw granulation techniques and present in detail their advantages and disadvantages. In addition, we discuss the detail of the instrumentation used for TSG and how the critical processing paraments (CPP) affect the critical quality attributes (CQA) of the produced granules. Finally, we present recent advances in TSG continuous manufacturing including the paradigms of modelling of continuous granulation process, QbD approaches coupled with PAT monitoring for granule optimization and process understanding.

A Semi-Mechanistic Prediction of Residence Time Metrics in Twin Screw Granulation

This work is concerned with the semi-mechanistic prediction of residence time metrics using historical data from mono-component twin screw wet granulation processes. From the data, several key parameters such as powder throughput rate, shafts rotation speed, liquid binder feed ratio, number of kneading elements in the shafts and the stagger angle between the kneading elements were identified and physical factors were developed to translate those varying parameters into expressions affecting the key intermediate phenomena in the equipment, holdup, flow and mixing. The developed relations were then tested across datasets to evaluate the performance of the model, applying a k-fold optimization technique. The semi-mechanistic predictions were evaluated both qualitatively through the main effects plots and quantitatively through the parity plots and correlations between the tuning constants across datasets. The root mean square error (RMSE) was used as a metric to compare the degree of goodness of fit for different datasets using the developed semi-mechanistic relations. In summary this paper presents a new approach at estimating both the residence time metrics in twin screw wet granulation, mean residence time (MRT) and variance through semi-mechanistic relations, the validity of which have been tested for different datasets.

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

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.