Accelerated Medicines Development using a Digital Formulator and a Self-Driving Tableting DataFactory
Abstract
Pharmaceutical tablet formulation and process development, traditionally a complex and multi-dimensional decision-making process, necessitates extensive experimentation and resources, often resulting in suboptimal solutions. This study presents an integrated platform for tablet formulation and manufacturing, built around a Digital Formulator and a Self-Driving Tableting DataFactory.
By combining predictive modelling, optimisation algorithms, and automation, this system offers a material-to-product approach to predict and optimise critical quality attributes for different formulations, linking raw material attributes to key blend and tablet properties, such as flowability, porosity, and tensile strength. The platform leverages the Digital Formulator, an in-silico optimisation framework that employs a hybrid system of models – melding data-driven and mechanistic models – to identify optimal formulation settings for manufacturability.
Optimised formulations then proceed through the self-driving Tableting DataFactory, which includes automated powder dosing, tablet compression and performance testing, followed by iterative refinement of process parameters through Bayesian optimisation methods. This approach accelerates the timeline from material characterisation to development of an in-specification tablet within 6 hours, utilising less than 5 grams of API, and manufacturing small batch sizes of up to 1,440 tablets with augmented and mixed reality enabled real-time quality control within 24 hours.
Validation across multiple APIs and drug loadings underscores the platform’s capacity to reliably meet target quality attributes, positioning it as a transformative solution for accelerated and resource-efficient pharmaceutical development.
Download the full article as PDF here: Accelerated Medicines Development using a Digital Formulator and a Self-Driving Tableting DataFactory
Materials
APIs used to produce quaternary and quinary mixture tablets are paracetamol (SP; Standard 6375, Mallinckrodt), acetylsalicylic acid (AS; Molekula), dexamethasone (DM; Powder, Molekula), griseofulvin (GR; Molekula), indomethacin (IM; Molekula), metformin hydrochloride (MH; Molekula). The tablet quaternary and quinary formulations incorporated several filler components, including microcrystalline cellulose with different grades (Avicel PH-101 and Avicel PH-102, DuPont Nutrition) and lactose (FastFlo 316, Foremost Farms USA). Additionally, a specific disintegrant, croscarmellose sodium (CCS) (AcDiSol, FMC International), was added into the formulation. To aid in the compression process, magnesium stearate (Hyqual 5712, Mallinckrodt) was used as a lubricant. Details regarding the characteristics of the excipients and API can be found in Table S1 in Supporting Information. These excipients were chosen to reflect some of the most commonly used materials in DC formulation in industry.
Accelerated Medicines Development using a Digital Formulator and a Self-Driving Tableting DataFactory,
Faisal Abbas & Mohammad Salehian, Peter Hou, Jonathan Moores, Jonathan Goldie, Alexandros Tsioutsios, Victor Portela, Quentin Boulay, Roland Thiolliere, Ashley Stark, Jean-Jacques Schwartz, Jerome Guerin, Andrew G. P. Maloney, Alexandru A. Moldovan, Gavin K. Reynolds, Jérôme Mantanus, Catriona Clark, Paul Chapman, Alastair Florence, Daniel Markl
Read also our introduction article on Disintegrants here:
