Pharmaceutical development faces a persistent challenge in that many active pharmaceutical ingredients (APIs) exhibit low aqueous solubility, limiting their bioavailability and therapeutic effectiveness. One of the most critical and least understood factors influencing these properties is crystal nucleation at interfaces. This process governs the transition from the amorphous to the crystalline state and impacts long-term stability, manufacturability, and drug release performance. Despite advances in solid-state chemistry, predictive control over interfacial nucleation kinetics in APIs remains limited due to the complexity of molecular interactions, the influence of thermodynamic and kinetic parameters, and the variability introduced by processing environments. The SMART project (“Smart Crystal Nucleation Near Interface Dynamics in Active Pharmaceutical Ingredients”) addresses this challenge by integrating molecular dynamics simulations, advanced kinetic modelling, and experimental electrochemical characterisation to establish a predictive framework for API crystallization. The project explores explicitly heteropolar graphene (HG) smart interfaces as a green, low-energy platform to control nucleation, enabling programmable crystallization kinetics with minimal environmental impact and aligning with EU strategic priorities in sustainable manufacturing, digitalisation, and the development of advanced materials for healthcare. The project’s objectives are to design dynamic models of API crystallization through simulation and modelling of API–interface interactions under varied thermodynamic and kinetic conditions, to identify and quantify kinetic models using both classical and adapted multivariate analysis methods, to experimentally validate theoretical predictions through non-isothermal and sub-glass-transition crystallization experiments correlating macroscopic crystallization rates with microscopic crystal growth patterns, and to develop smart analytical tools for predictive stability by combining in silico and experimental techniques to create reliable, low-carbon-footprint protocols for monitoring and controlling crystallization. The pathway to impact is based on a closed-loop model in which computational insights inform experimental design, reducing trial-and-error, resource consumption, and time-to-market for stable drug formulations. Outcomes from SMART are expected to advance scientific understanding of interfacial dynamics in pharmaceutical crystallization, enable sustainable manufacturing by introducing green synthesis routes and low-energy crystallization control methods, enhance drug stability and bioavailability through interface-engineered control over crystallization. The scale and significance of these impacts extend across pharmaceutical research and development, manufacturing efficiency, and patient outcomes, as predictive, programmable control of crystallization will help reduce development costs, minimise waste, and accelerate the delivery of effective medicines to market. Given the project’s inherently multidisciplinary nature, social sciences and humanities perspectives, particularly in the context of sustainable innovation and regulatory acceptance play a role in framing the adoption of green materials and advanced manufacturing methods in the pharmaceutical industry, ensuring that the technical advances align with societal expectations, ethical considerations, and health policy priorities, thereby maximising real-world uptake and long-term benefits.
