Issue link: https://www.e-digitaleditions.com/i/1173734
26 October 2019 Tablets & Capsules Advantages of fluid-bed technology C ont inuou s s ystems c an avoid the challenges associated with twin-screw granulators by using flu- id-bed processing instead. In a fluid-bed processor, granulation and dr ying can occur in the same pro- cess chamber, eliminating the need to transfer wet granulated material and improving system reliability. Fluid-bed granulation allows manufacturers to achieve unimodal particle size distributions, excellent flow and tableting properties, and higher production yields. Using the f luid-bed g ranulation process for exist- ing products also eliminates the need for technology transfer, which makes changing from batch to continu- ous processing significantly easier. Systems can apply the same principle of dosing as a discrete mass to the external phase. In the final processing step, tableting takes place in an integrated tablet press. Connection to line controls and a flexible filling-height control ensure smooth operation, while wash-in-place (WIP) nozzles ensure fast and largely automated cleaning. Fit for the future Transferring traditional batch processes such as the top-spray process from the laboratory to production is often a challenge for pharmaceutical manufacturers. Continuous processing eliminates this inherently risky and time-critical stage. Manufacturers can develop new products using suitable R & D equipment or a continuous platform such as the Xelum system that features an integrated automatic design of experiments (DoE) function and software equipped with the rele- vant test-automation support functions. Continuous SODF manufacturing will take on an important role alongside batch production. Manufacturers must decide which method to use on a product-by-prod- uct basis, keeping in mind that not all continuous processes are the same. Platforms such as the Xelum system are not limited to wet granulation and tableting but are also conceived for applications such as direct compression tableting. These systems offer an industry-4.0-ready, eco- nomical alternative to batch production and are constantly being refined to meet future industry requirements. T&C Fritz-Martin Scholz (+49 7622 6884 131, fritzmartin.scholz@ bosch.com) is product manager at Bosch Packaging Technology (www.boschpackaging.com), a leading provider of process tech- nology and packaging solutions to the pharmaceutical industry. wet granulation operate in batch mode and must be mod- ified for continuous production. Cur rent continuous production systems for wet g ranulation usually rely on continuous t win-screw granulators, with the subsequent fluid-bed drying usu- ally occurring via a package-per-package approach in separate chambers, to control the material's residence time and expose all the particles to the same amount of drying energy. T h e b i g g e s t c h a l l e n g e f o r t o d a y 's c o n t i n u - o u s pr o d u c t ion s ys te ms is pr e cis ely d o sing the starting materials. Systems must continuously dose active ingredients and excipients at constant mass flow rates in the range of milligrams per second. Because all currently available dosing systems exhibit fluctuations in the achievable mass flow rate over time, it's man- datory to check the API content online using process analytical technology (PAT). Back mixing is the only way to compensate for these flow rate fluctuations, but this broadens the material's residence time distribution in the system, making traceability more difficult. In addition, current continuous systems require a startup phase before achieving steady-state operation, which results in startup and shutdown losses. Another challenge of continuous processes that include twin-screw granulation is that the granule den- sity can change over time and the material often has a bimodal particle-size distribution. This might cause particle-size segregation, which can have a negative effect on tablet properties in certain circumstances and is something that manufacturers should consider when transferring technologies. A s these challenges show, continuous phar ma- ceutical production still has room for improvement. However, new technologies such as Bosch Packaging Technology's Xelum platform are demonstrating that these challenges can be overcome. Reducing complexity One solution to improve dosing accuracy is to dose APIs and excipients as discrete masses rather than using continual mass flow. This allows precise dosing of even the smallest API amounts. The system doses and mixes the ing redients in individual packages, which continuously run through each step of the pro- cess chain and are removed successively. This reduces both the process complexity and the system's suscep- tibility to failure, which increases the consistency and quality of the end product. This also makes it easier to measure the necessary critical quality attributes, in part, using soft sensors. Because the system does not require steady-state oper- ation, startup and shutdown losses are eliminated. All starting materials can be traced back along the produc- tion line and clearly matched to the final dosage form, as back mixing occurs only within each individual package.