Fully Automated & DoE-Based Development of an Oral Solid Dosage Form

Synopsis

Goal of the presented study and data is to demonstrate the potential of a fully automated and DoE-based development of new oral solid dosage form (tablet). The combination of DoE and automated execution of each process step offer a new potential to speed up and integrate more quality-in-design in the development process.
All development steps were planned by Design of Experiment. For the granulation an automated fluid granulation module was used. All different powder granules were compressed on rotary tablet press with an integrated and automated change of 2- and 3-paddle-feeder and other compression parameters. All tablets were analyzed on an automated WHT with integrated micro-wave based weight measurement and NIR-based content uniformity measurement.
With a semi-continuous fluid bed granulation module 26 different lots of fluid-bed granules with different API-content, humidity and process parameter were prepared. The 26 lots were then automatically compressed on rotary press with different process parameter and an automated 2 and 3-paddle-feeder and wing change to get more than 200 different tablet lots (each > 500 tablets). All of the tablets were than characterized on a new high-throughput-inspection machine with weight, hardness, dimensions and content uniformity. Based on the large number of samples with different process parameter the influences and interaction of materials, recipe and formulation with the process parameter of granulation and compression were analyzed.
Based on the automation of all development steps (granulation, compression and quality analysis) a high throughput and short development time was achieved. Based on 26 formulations, more than 200 tablets lots were prepared, each of them more than 500 tablets. All tablets were tested on a new tablet analysis tool, measuring weight, dimension and API content. By the combination of DoE and automation it’s possible to screen a larger parameter space, identify interaction of parameters and optimize the quality of the tablets. By the automation also the required amount of material is less than by a manual testing and change of the different modules like 2- and 3-paddle-feeder.