Traditional methods of developing drug products for a new active pharmaceutical ingredient are time-consuming, costly and often inflexible. The selection of the right excipients in tablets and process conditions are crucially important as they can impact manufacturability, performance and stability of the drug product. Formulation optimization studies are conducted to identify a robust formulation that can meet manufacturability criteria (e.g. flowability, tensile strength) while fulfilling the desired performance targets, e.g. release of > 80% of the drug in less than 30 min. This is a multidimensional problem with a high degree of interdependence between raw material attributes, process parameters, and drug product properties. These complex relationships cannot be fully captured by first principle models and it is not feasible, in a reasonable time, to experimentally investigate these multidimensional formulation (type of excipient, concentration, drug loading) and process parameter (e.g. compression force, dwell time) spaces following traditional experimental planning and methods. This work presents a high-throughput data-intensive micro-scale tablet development system that can automatically prepare and measure powder, and produce and test single tablets. All the devices involved in the system are fully integrated digitally and physically realising system that can automatically adapt process conditions and parameters in real time. The system consists of an automated dosing unit that discharges the powder for one single tablet. The powder is transported by a bespoke transportation unit (TU) attached to a robotic arm. The TU is designed in a way that allows no physical connection with the robot for precise powder weight measurement. The homogeneity of the powder blend is measured using near infrared (NIR) spectroscopy through a sapphire glass window at the bottom of the TU. The TU discharges the powder into the die of a compaction simulator that produces the tablet. An automated testing system collects the tablets from the tablet press for weight, dimensions, and breaking force measurements. Finally, the tablets are picked up by a robot and placed at sessile drop system for the measurement of liquid uptake and swelling kinetics of the tablet to gain information about the performance.
The performance of the overall automated system is validated and benchmarked by feeding the system with a list of pre-defined process parameters. The tablet development system executes the list of experiments automatically and extracts, transforms, and loads the data into a structured database including the metadata associated to the experiment. This data can directly be accessed and utilised by other digital systems, such as data-driven models for predicting tablet properties. The system is capable of manufacturing and testing 120 tablets per hour that includes a complete walk through all the aforementioned devices. This reduces the hands-on-lab time by > 80% and minimises human error significantly. This fully automated will deliver the data needed for transformative data-driven and hybrid digital twins connecting raw materials to tablet attributes. The combination of the automated development system with real-time digital twins will reduce development times and the use of raw materials/solvents while achieving quality objectives through self-optimised formulation and process conditions.
