Digital Design and Manufacture of Amorphous Pharmaceuticals (DDMAP)

Lead Research Organisation: University of Strathclyde
Department Name: Inst of Pharmacy and Biomedical Sci

Abstract

The Digital Design and Manufacture of Amorphous Pharmaceuticals (DDMAP) Centre will create a new international collaboration bringing together a world-leading group of researchers from the UK (University of Strathclyde), Denmark (University of Copenhagen) and Belgium (Ghent University) to deliver a step change in fundamental understanding of amorphous materials in order to apply to real industrial challenges in medicines manufacturing. Amorphous materials are different from the crystalline materials commonly used in medicines and offer substantial opportunities to address challenges in current products including improved processing, stability and overall performance in patients.

The centre's will address key research questions that underpin the selection, production and application of amorphous molecular solids in medicines development and manufacture. Research is split across four work packages, WP1-4:

WP1 will establish a unique Amorphous Pharmaceuticals Database (APDb) as a research platform to share data across the project, inform model development and disseminate data with the wider community. Specific research aims include establishing a predictive Amorphous Stability Index (ASI) for drug molecules and to investigate the solid-state structure of amorphous drugs as well as co-amorphous and drug-polymer systems using techniques including X-ray PDF, modelling and refinement approaches. This work will allow us to better understand how these materials behave and how best to exploit them in manufacturing processes.

WP2 will develop predictive methodologies and tools for right-first-time amorphous pharmaceutical processing via Hot Melt Extrusion (HME), the process of applying heat and pressure to melt a material, and subsequent dose form processing steps including compression and 3D printing. The team will exploit advanced continuous processing and analytical capabilities available across all three partners and through powerful x-rays, to investigate transformations and stability of amorphous materials during key secondary processing steps such as milling, compaction, drying and additive manufacturing.

WP3 will investigate the mechanisms and structural changes of drug release from amorphous dosage forms in biorelevant media, e.g. that simulate stomach and intestinal fluids, to develop models for performance prediction of amorphous solid dosage forms in patients. Drawing on progress in WP1 and 2 the extensive dissolution and analytical capabilities across the international partners will identify drug release mechanisms and physical transformations that occur in systems during use. We will modify composition and structure to achieve control over release.

WP4 will be managed by the project team to strengthen collaboration across the researchers and partners through sharing data, training, best practices and learning. Mobility and knowledge exchange between centres will be promoted through Faculty and Researcher exchanges with face-to-face progress meetings rotating round centres. Regular virtual meetings will be used to agree plans and track progress. Digital tools (MIRO, Electronic Laboratory Notebooks - ELN) and data management plans will ensure ongoing comms across DDMAP and a digital comms plan will ensure timely dissemination of outputs and outcomes with the international academic and industrial communities. Industrial case studies that integrate outputs from WP1-3 will be disseminated and promoted globally through networks, social media and virtual events anticipated to outreach to tens of thousands based on current network reach analytics. These include examples such as an open access database for amorphous materials (APDb) and access to developed amorphous indexing tool.

Publications

10 25 50
 
Description Key findings to date have focused on the development of new automated workflows for screening of amorphous and multi-component amorphous pharmaceuticals providing data rich results for inclusion in an amorphous pharmaceutical database. This allows for the efficient and effective development of processes, gaining process understanding, saving time, reducing risk and reducing resource requirements in the development of multi-component amorphous pharmaceutical systems. A stability screening platform has been developed to monitor amorphous stability over time giving insight into future manufacturing properties during processing. This has been verified to provide manufacturability and stability information on processing through hot melt extrusion case studies. The use of Optical Coherence Tomography (OCT) via dissolution experiments of extrudate has also provided insight into mechanistic understanding of the structural changes during drug release from amorphous dosage forms.
Exploitation Route The outcomes of this project will produce vital information for pharmaceutical industry to gain better understanding on the use and stability of amorphous pharmaceuticals, offering substantial opportunities to address challenges in current products including improved processing, stability and overall performance in patients. This may be progressed through the industry partners of the project, but will also be amplified through the other CMAC Tier 1 membership of eight large pharma including AstraZeneca, Chiesi, Lilly, Pfizer, Roche, Sanofi, Takeda, UCB.
Sectors Pharmaceuticals and Medical Biotechnology

 
Description Membership of the Skills subgroup of Medicines Manufacturing Industry Partnership (MMIP)
Geographic Reach National 
Policy Influence Type Participation in a guidance/advisory committee
Impact MMIP has identified six objectives for medicines manufacturing skills in the UK: 1: Promote the Medicines Manufacturing Industry and careers within it 2: Create apprenticeships standards to enable companies to use the Apprenticeship Levy 3: Share and promote good practice for training and skills development 4: Address the low level of practical skills in graduates and other new-starters 5: Address the issues arising from there being relatively small national cohorts for education and training in a number of critical skills areas 6: As part of the ATMP Taskforce recommendations, deliver an End to End Talent Management Plan for the sector and establish a Skills and Training Academy for the UK
URL https://www.abpi.org.uk/r-d-manufacturing/medicines-manufacturing-industry-partnership-mmip/
 
Description Co-Processing of Amorphous Solid Dispersions via Co-Precipitation
Amount £92,668 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 09/2023 
End 03/2027
 
Description Framework to Rational Amorphous API Development
Amount £135,871 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 09/2023 
End 09/2027
 
Description Knowledge Transfer Partnership (KTP): Pair Distribution Function (PDF) Analysis
Amount £195,360 (GBP)
Funding ID Ref No 10013866 (KTP No 13050) 
Organisation AstraZeneca 
Sector Private
Country United Kingdom
Start 08/2022 
End 09/2024
 
Description Prediction of Manufacturability and Transformations During Amorphous Pharmaceuticals Processing
Amount £84,491 (GBP)
Organisation University of Strathclyde 
Sector Academic/University
Country United Kingdom
Start 09/2022 
End 03/2026
 
Description Prediction of Structure of Amorphous Pharmaceuticals
Amount £85,139 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 09/2022 
End 03/2026
 
Description Saltire Emerging Researcher Visits
Amount £5,800 (GBP)
Organisation The Scottish Universities Physics Alliance (SUPA) 
Sector Academic/University
Country United Kingdom
Start 04/2022 
End 07/2022
 
Description Astrazeneca 
Organisation AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution Undertaking research that has outputs relevant to the industry partners
Collaborator Contribution AstraZeneca are providing expertise and intellectual input to the direction of the research project through discussions at project meetings.
Impact None yet.
Start Year 2022
 
Description Cambridge Crystallographic Data Centre 
Organisation Cambridge Crystallographic Data Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution Undertaking research that has outputs relevant to the industry partners
Collaborator Contribution CCDC are providing expertise and intellectual input to the direction of the research project through discussions at project meetings.
Impact none yet
Start Year 2022
 
Description Collaboration with the ISCF Digital Design Accelerator Platform (DDAP) 
Organisation AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution Project name: Digital Design Accelerator Project to Connect Active Material Design to Product Performance Provided models and data for the development of new tools on the project. Provided software development capacity via ARTICULAR RAs.
Collaborator Contribution Data were provided to validate our AI models (large pharma: AZ, GSK, Pfizer). Partners provided end users to test our tools and interfaces.
Impact New data analysis and handling capabilities that can work with data across pharmaceutical organisations
Start Year 2019
 
Description Collaboration with the ISCF Digital Design Accelerator Platform (DDAP) 
Organisation GlaxoSmithKline (GSK)
Department Research and Development GSK
Country United Kingdom 
Sector Private 
PI Contribution Project name: Digital Design Accelerator Project to Connect Active Material Design to Product Performance Provided models and data for the development of new tools on the project. Provided software development capacity via ARTICULAR RAs.
Collaborator Contribution Data were provided to validate our AI models (large pharma: AZ, GSK, Pfizer). Partners provided end users to test our tools and interfaces.
Impact New data analysis and handling capabilities that can work with data across pharmaceutical organisations
Start Year 2019
 
Description Collaboration with the ISCF Digital Design Accelerator Platform (DDAP) 
Organisation Pfizer Ltd
Country United Kingdom 
Sector Private 
PI Contribution Project name: Digital Design Accelerator Project to Connect Active Material Design to Product Performance Provided models and data for the development of new tools on the project. Provided software development capacity via ARTICULAR RAs.
Collaborator Contribution Data were provided to validate our AI models (large pharma: AZ, GSK, Pfizer). Partners provided end users to test our tools and interfaces.
Impact New data analysis and handling capabilities that can work with data across pharmaceutical organisations
Start Year 2019
 
Description Lek Pharmaceuticals 
Organisation Novartis
Department Sandoz
Country Germany 
Sector Private 
PI Contribution Undertaking research that has outputs relevant to the industry partners
Collaborator Contribution Lek Pharmaceuticals are providing expertise and intellectual input to the direction of the research project through discussions at project meetings. They are also contributing material for experiments.
Impact none yet.
Start Year 2022
 
Description Takeda 
Organisation Takeda Pharmaceutical Company
Department Takeda Pharmaceuticals U.S.A., Inc. (TPUSA)
Country United States 
Sector Private 
PI Contribution Undertaking research that has outputs relevant to the industry partner
Collaborator Contribution Takeda are providing expertise and intellectual input to the direction of the research project through discussions at project meetings
Impact None yet
Start Year 2023
 
Description University of Copenhagen 
Organisation University of Copenhagen
Country Denmark 
Sector Academic/University 
PI Contribution Expertise and intellectual input, access to data, equipment and facilities.
Collaborator Contribution CPharma, University of Copenhagen are providing expertise and intellectual input, access to data, equipment and facilities.
Impact Contribution to project discussions and steering research.
Start Year 2022
 
Description University of Ghent 
Organisation University of Ghent
Country Belgium 
Sector Academic/University 
PI Contribution Expertise, intellectual input, access to data equipment and facilities.
Collaborator Contribution CESPE, University of Ghent are providing expertise, intellectual input, access to data equipment and facilities.
Impact Contribution to early project discussions.
Start Year 2022
 
Description Amorphous APIs, drug product intermediates and drug products - Challenges and opportunities 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Project team visited AstraZeneca to discuss research and outcomes to date and potential future collaborations with the company.
Year(s) Of Engagement Activity 2023
 
Description CMAC Reseachers visit to University of Copenhagen (CPH) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact DDMAP team visited University of Copenhagen to disseminate current research and discuss opportunities for research exchanges to accelerate the outputs of the project.
Year(s) Of Engagement Activity 2023,2024
 
Description Doors Open Glasgow 2022 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact CMAC are participated in the #Glasgow Doors Open Days Festival (https://glasgowdoorsopendays.org.uk) Saturday 17th September 2022 (10am-4pm) at the Technology & Innovation Centre (TIC), University of Strathclyde.
Year(s) Of Engagement Activity 2022
URL https://glasgowdoorsopendays.org.uk/building-no-booking/technology-innovation-centre-tic-university-...
 
Description EPSRC 's Executive Chair, Lynn Gladden visit & blog mention 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact In a new blog post, the EPSRC 's Executive Chair, Lynn Gladden, reflects on her university visits, including a visit to CMAC at University of Strathclyde. It was a pleasure to host Lynn as part of this tour, showcasing our facilities and discussing how CMAC can work with UKRI to 'transform tomorrow together'.
Year(s) Of Engagement Activity 2022
URL https://bit.ly/3Du7kgM
 
Description Hosted visitors from Bristol Myers Squibb & Malvern Panalytical 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact CMAC were delighted to host visitors from Bristol Myers Squibb & Malvern Panalytical @newsfrom_MP 17th Aug 2022. Mike Tobyn (Senior Scientific Director at Bristol-Myers Squibb) gave an engaging seminar to the CMAC community titled Small Particles and Big Data.
Year(s) Of Engagement Activity 2022
 
Description New CMAC Industry Board Chair - Dr Ivan Marziano 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact CMAC announced the new chair of the CMAC Industry Board by press release on the CMAC website and Twitter.
Year(s) Of Engagement Activity 2022
URL https://cmac.ac.uk/news-database/a-new-chapter-for-cmacs-industry-board
 
Description Participation at CMAC Open Days, 14-16 November 2023 (Organiser) 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Research related conference to engage stakeholders and build network across CMAC research portfolio. Future CMAC Hub and aligned projects posters, showcases, lab tours and talks; DM2 demonstration of research progress to date and it's researchers present talks and posters. Some talks on the YouTube Channel: https://www.youtube.com/channel/UCbic3O4IH1TLMhExyY9Utmg.
Year(s) Of Engagement Activity 2023
URL https://cmac.ac.uk/events-database/open-days-2023
 
Description Queen's Anniversary Prize 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact CMAC were honoured to be part of the University of Strathclyde's team that received the Queen's Anniversary Prize for Higher and Further Education at St James's Palace on 23rd Feb 2022 for our excellence in Advanced Manufacturing. The university and CMAC have posted this on their websites.
Year(s) Of Engagement Activity 2022
URL https://cmac.squarespace.com/news-database/qap
 
Description Robotics Fair at Strathclyde 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Jan 25 2023: CMAC researchers Chantal Mustoe and Faisal Abbas took part in a Robotics Industry Fair at the University of Strathclyde. This was a great opportunity to showcase their work with robotics as part of our DataFactories and Digital Medicines Manufacturing programmes.
Year(s) Of Engagement Activity 2023
 
Description School Visit (Inverness) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Visit to local school as part of STEM week visiting 3 classes (75 children total) to discuss medicine manufacturing and conduct short experiments to engage children in the topic.
Year(s) Of Engagement Activity 2023,2024
 
Description Scotland House Office Opens 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact CMAC are take up residence at Scotland House, London, UK on 29/04/2022. We're delighted to introduce the new CMAC Central London Office. Press release on website.
Year(s) Of Engagement Activity 2022
URL https://cmac.ac.uk/news-database/cmac-london-office
 
Description Scottish Secretary of State visit 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Policymakers/politicians
Results and Impact CMAC were happy to show Scottish Secretary of State, Lord Offord of Garvel, around our world-leading facilities at the end of July 2022 as part of his broader visit to University of Strathclyde.
Year(s) Of Engagement Activity 2022
 
Description Visit by MP Carol Monaghan 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Policymakers/politicians
Results and Impact CMAC hosted MP Carol Monaghan on 5th October 2022 (@CMonaghanSNP) and showcased all the innovative medicines manufacturing research being carried out by CMAC here in Glasgow.
Year(s) Of Engagement Activity 2022
 
Description Visit by Parliamentary Under Secretary of State (Minister for Small Business, Consumers and Labour Markets) 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Policymakers/politicians
Results and Impact 17/02/2022: CMAC host UK were thrilled to host Parliamentary Under Secretary of State (Minister for Small Business, Consumers and Labour Markets), @scullyp this week and provide a tour of our facilities highlighting #CMACs vision to transform #medicines development, manufacture and supply.
Year(s) Of Engagement Activity 2022
 
Description Webinar on the #FutureOfWork in Medicines #Manufacturing 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact @ESRC @InterActNetw0rk collaborated with CMAC to host a webinar on the #FutureOfWork in Medicines #Manufacturing, Thursday 12 January, 2023. Traget audience members: people manager or workplace stakeholder in the sector.
Year(s) Of Engagement Activity 2023
URL https://linkedin.com/pulse/digital-medicines-manufacturing-future-work-webinar-lindsay-mcipd-/