The pharmaceutical industry has several challenges that hinder the development and manufacture of new drug formulations of bioavailable medicines efficiently and sustainably. Indeed, poor bioavailability affects 70-90% of pipeline drugs and 40% of marketed medicines, contributing to estimated 17% of Phase-I clinical trial failures. One of the common strategies to address this problem is the use of Amorphous Solid Dispersions (ASDs), which improve drug solubility and bioavailability. However, ASD manufacturing processes, such as spray drying, are resource-intensive, may use toxic solvents, consume high energy, and could cause substantial loss of expensive active pharmaceutical ingredients (APIs) during scale-up. Furthermore, there is no assurance regarding the product's performance in human which may require adjustments and rework of formulations. Thus, we are proposing end-to-end integration of advanced digital molecular models with dosage form manufacturing and product performance pharmacokinetic models. Utilising tools developed by consortium partners, we will digitize the solid dosage form formulation process with a focus on ASDs to optimise formulation stability, solubility, drug loading, solvent selection, secondary processing and final performance in clinical bioavailability studies. The integration of these models with Good Manufacturing Practice (cGMP) processes ensures efficient scalability from small- to large-scale production. This also includes efforts by consortium partners to innovate and champion new advanced green analytical methods as analytics continue to be a bottleneck in the development and quality assurance of new products. Ultimately, the consortium goal is to reduce toxic solvent usage by 50%, cut energy consumption by 30%, and improve API utilization, promoting more sustainable drug development. This proposal aligns with Net Zero goals of the UK government, the pharmaceutical industry and the NHS. It also helps in the efforts to reach global sustainability goals, as the pharmaceutical sector currently contributes 4.4% of global emissions, equivalent to the output of 514 coal-fired power plants. By reducing waste, emissions, and energy consumption, this project will help minimize the environmental footprint of pharmaceutical manufacturing while accelerating drug development and improving production efficiency. By developing an integrated platform that brings multiple novel solutions in an innovative way, the consortium will ensure efficient transition in pharmaceutical development from formulation screening to full-scale production, reducing the process time to few weeks. This positions the UK as a leader in sustainable pharmaceutical manufacturing, advancing medicine supply chain security, public health and prioritises environment protection and alignment with Net Zero goals.

Long-acting injectable (LAI) drug products offer the potential to transform human health through treatment of a range of diseases. Most of LAI research to date has been invested in exploring new APIs and novel drug cargoes for improved therapeutic effect and better patient compliance. This has led to limited research exploring the science underpinning the medicine manufacturing of LAI drug products. A key challenge is that product attributes, e.g., release profile, are sensitive to manufacturing process, affecting performance and quality of end-products. In addition, lack of reference product characterisation further hampers the bench-to-clinic translation of LAI drug products. To untangle these challenges, in-depth characterisations which can establish the link between products' critical quality attributes (CQAs) and manufacturing process parameters are required. There is also a need to develop virtual bioequivalence(BE) testing to enhance LAI formulation's in-vitro/in-vivo correlations. We will develop the world's-first accelerated 'Process-to-PK' LAI platform, integrating microsphere manufacturing processes, product CQAs, predictive release kinetics, and mechanistic pharmacokinetic/BE models. Compared to the conventional homogenisation, our platform can provide more efficient, reproducible and scalable manufacturing process to achieve excellent formulation uniformity. In addition, this evidence-based, data-driven manufacturing platform will significantly reduce the risks in LAI product development and facilitate decision making by linking early-stage manufacturing outcome with later-stage pharmacokinetics with minimum resources requirements. Our work will be the first in the market to link a manufacturing process with in-depth microsphere's CQA characterisation and formulation fate in human-relevant mechanistic PK models. De-risking the complex development of LAIs will lead to more cost-effective therapies, ultimately providing patients and the NHS with treatment options.

_**ASD3MAP: Amorphous Solid Dispersion Digital Design and Manufacturing Platform for rapid and resource-efficient development of bioavailable medicines.**_ MESOX Ltd (Lead), in collaboration with Aston University (Partner), propose an 18-month project focussing on the refinement of the Consortium's molecular dynamics models through the integration of at market material science and simulation tools to deliver an advanced in-silico formulation development platform for amorphous solid dispersions (ASDs). Furthermore, we will integrate the generated modelling data with thermodynamics and novel computational fluid dynamics (CFD) models to predict the impact of cGMP manufacturing scale-up on the formulation.

MESOX developed a novel particle carrier technology for enhancing the bioavailability of medicines. The carrier has nanopores within its structure and each nanopore behaves like a nano-container for drug molecules. When a drug is loaded within a nanopore, it converts to its amorphous solid form which easily dissolves in the patient body. As a result, drug efficacy could be enhanced due to better absorption, and lower doses would be required as opposed to the drug in its native state without our carrier. In line with the developed carrier, we have also built a molecular model of the carrier which allows us to screen drugs virtually on a computer prior to conducting laboratory experiments. This provides two key advantages to potential pharma and biotech customers: 1- Saves their precious drug through avoiding extensive experimental formulation work. 2- Provides quick feedback on the feasibility of our carrier technology for their drug molecule. However, a key to unlocking the power of this molecular model is to validate its observations using an advanced analytical technique. A technique is needed that can quantify the amount of drug within carrier (maximum amount that can be loaded), nature of drug loaded within carrier (molecular interactions, amorphous/crystalline phase) and preserves the carrier structure during the analysis process (for reliable results). The national physical laboratory will assist us with an advanced analytical technique that meets the above criteria for model validation. Our modelling capability once validated will represent a leap forward in formulation development science. It will help reduce the risks of the formulation process leading to lower product costs, and accelerate the timelines for the development of new medicines. Ultimately, this approach could lead to more lifesaving medicines getting into patients' hands quicker and saving the NHS and the UK taxpayer millions of pounds in healthcare costs.

We propose to develop a novel medicated dressing containing a molecule that achieves faster diabetes wound healing. This is a problem affecting 450,000 individuals with diabetes in the UK alone. It costs the NHS £900M annually in care (healthcare visits) and treatment costs (antibiotics, bandages etc). We expect our dressing to be able to achieve twice as faster wound healing following diabetic pressure ulcers formation. This is because the molecule contained within is capable of encouraging faster growth of epithelial skin tissues at the affected wound site. This could lead to faster recovery from this debilitating complication and less risk for infection, sepsis and amputations. When pressure ulcers develop, patients could easily apply our dressing onto the affected area and recovery should be much quicker than traditional dressings. We expect to save the NHS £350M annually in costs related to out-patient and primary care costs using our innovation. The funding from IVUK will allow us to develop a product that is both affordable to the NHS and represents good value for money for UK taxpayers. The primary beneficiaries will be patients living with diabetes and suffering from its complications as well as NHS which is already under immense cost and capacity pressures.