Understanding pharmaceutical film coating process using combined optical coherence tomography and terahertz in-line sensing
Lead Research Organisation:
Lancaster University
Department Name: Engineering
Abstract
Functional coatings are highly engineered drug delivery systems whose structure and composition are critical to the controlled release of the active pharmaceutical ingredient in the human body. These products are at the high value end of the market and represent sophisticated solutions to difficult disease management. Manufacturing these products is challenging largely because pharmaceutical processing is complex that has traditionally been dominated by empirical understanding. The increase in manufacturing complexity coincides with the paradigm shift that the pharmaceutical industry is facing today where emphasis is now being placed on fostering a greater product and manufacturing understanding for building quality into the product and enable continuous manufacturing. Building on the recent successful demonstration of combined optical coherence tomography and terahertz real-time sensing for a coating process where an unprecedented level of in-process diagnostic information were obtained, we will now perform systematic coating process investigation to quantify and model the effects of the key process parameters. The developed data-driven models will in turn allow us to identify the optimal process conditions for validation against science-based process modelling, which can then be used to explain process observations. Ultimately, enhanced process understanding will enable the development of model-based predictive control for the full implementation of continuous manufacturing for producing next generation pharmaceutical products. This project will be supported by a world leading supplier of manufacturing equipment (Bosch, Germany), academic technology collaborators (University of Cambridge, UK and University of Liverpool, UK) and coating materials suppliers (BASF, UK and Colorcon, UK).
Planned Impact
Pharmaceutical film coatings serve the very purpose of protecting the active ingredient from light and moisture, thereby improving the shelf-life of the dosage forms. Coatings can also serve the purpose of improving the aesthetics and taste masking. For advanced dosage forms, coatings serve a functional purpose as in the case of active coating or it can be used to control drug release, thereby determining the therapeutic efficacy of the drug. The lack of fundamental process understanding currently hinders the production of advanced dosage forms on a consistent quality basis. An improved process understanding will have an immediate impact on coating equipment manufacturers by suggesting possible design changes to enhance coating efficiency. It would also recommend methods of deploying process analytical technologies for process monitoring. Process understanding will also impact pharmaceuticals and coating materials suppliers, in terms of optimising process and control leading to reduced waste and improved product performance. The interdisciplinary nature of the project will expose the industry to cutting-edge process analytical technologies, novel methods of data interpretation and modelling, while at the same time, provide an unique opportunity for young researchers to work at the forefront of pharmaceutical science and process analytical technologies, and to develop advanced skills that are essential for UK research and business. This research will therefore be supported by a world leading coating equipment manufacturer (Bosch, Germany) and coating materials suppliers (BASF, UK and Colorcon, UK). At an industry wide level, this work will generate a substantial body of new academic knowledge that coincides timely with the paradigm shift that the pharmaceutical industry is facing today as it moves from the traditional quality by testing to quality by design, where the focus is on product and manufacturing understanding. The knowledge gained would in turn inform the regulators on the best practices. In the longer term, this work would enable the development of active control strategies as part of the full implementation of continuous manufacturing in order to facilitate the production of advanced dosage forms on a consistent quality level basis efficiently. This would in turn have impact across a very wide range of communities both economically and societally, especially as these dosage forms represent sophisticated solutions to difficult disease management.
Publications
Zhang Z
(2019)
Sub-surface imaging of soiled cotton fabric using full-field optical coherence tomography.
in Optics express
Alves-Lima D
(2020)
Quantitative video-rate hydration imaging of Nafion proton exchange membranes with terahertz radiation
in Journal of Power Sources
Alves-Lima D
(2020)
Review of Terahertz Pulsed Imaging for Pharmaceutical Film Coating Analysis
Alves-Lima D
(2020)
Review of Terahertz Pulsed Imaging for Pharmaceutical Film Coating Analysis.
in Sensors (Basel, Switzerland)
Alves-Lima D
(2020)
Review of Terahertz Pulsed Imaging for Pharmaceutical Film Coating Analysis.
Description | We have developed a methodology using machine learning algorithms to automatically classify waveforms acquired in real-time by a terahertz sensor (terahertz pulsed imaging) of a production scale pharmaceutical tablet coating process. This approach relies on a database of already acquired terahertz waveforms of coated tablets and can significantly increase the number of measurements than previously using thresholds. This improvement in turn can be used to for real-time waveform detections and reveal changes to coating thickness distribution occurring during coating operation enabling systematic process investigation. In parallel, using compact terahertz source and camera, we have developed a simple system to quantitatively image water and have imaged polymer electrolyte membranes used in fuel cells. Results of which, have been benchmarked against simultaneous gravimetric analysis. Update Mar 2022: We further demonstrated the possibility to resolve detailed water information in industrially relevant thin membranes resulting using terahertz spectroscopy. |
Exploitation Route | This is an ongoing process and we are still in active dialogue with potential end users as well as equipment manufacturers who are interested in adapting our approach. |
Sectors | Chemicals Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |
Description | We have had a industry engagement with Johnson Matthey where we presented our research outcomes to them. We have further secured an EPSRC H2FC Supergen Flexible Grant to extend the technology for industrially applicable membranes as part of UK industrial strategy. Update 03/2023, we have delivered an invited talk at H2FC Supergen, Condensed Matter Physics Seminars at University of Warwick, received a Royal Academy of Engineering Industrial Fellowship, Impact Acceleration Account, EPSRC Vacation Internship and a CASE Award. |
First Year Of Impact | 2020 |
Sector | Chemicals,Manufacturing, including Industrial Biotechology |
Impact Types | Cultural Economic |
Description | H2FC Supergen Flexible Funding |
Amount | £99,671 (GBP) |
Organisation | Hydrogen and Fuel Cell Supergen |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2020 |
End | 10/2021 |
Title | Quantitative video-rate hydration imaging of Nafion proton exchange membranes with terahertz radiation |
Description | The data was used to produce the figures in the linked publication and it consists of the data for the individual figures. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | These experimental data are currently used for benchmarking against dataset generated using improved techniques. |
URL | http://www.research.lancs.ac.uk/portal/en/datasets/quantitative-videorate-hydration-imaging-of-nafio... |
Title | Sensing water absorption in hygrothermally aged epoxies with terahertz time-domain spectroscopy |
Description | Supporting data for http://dx.doi.org/10.1021/acs.analchem.0c04453Description |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | These experimental data are being used to infer the dielectric response of similar epoxy based material and response to hygrothermal conditioning. |
URL | http://www.research.lancs.ac.uk/portal/en/datasets/sensing-water-absorption-in-hygrothermally-aged-e... |
Title | Through-substrate terahertz time-domain reflection spectroscopy for environmental graphene conductivity mapping |
Description | The data was used to produce the figures in the linked publication and it consists of the data for the individual figures. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | These experimental data are currently being used by collaborators to assess graphene quality. |
URL | http://www.research.lancs.ac.uk/portal/en/datasets/throughsubstrate-terahertz-timedomain-reflection-... |
Description | BASF coating materials |
Organisation | BASF |
Country | Germany |
Sector | Private |
PI Contribution | We are performing tablet mixing trials monitored using terahertz and optical sensors. |
Collaborator Contribution | BASF has provided batches of coated pharmaceutical tablets as sample specimens for this project. |
Impact | Xiaoran's IRMMWTHz |
Start Year | 2019 |
Description | Bosch Packaging Technology |
Organisation | Robert Bosch Foundation |
Country | Germany |
Sector | Charity/Non Profit |
PI Contribution | We developed and deployed a simple, compact inline OCT sensor to monitor a commercial fluidised bed coating process. |
Collaborator Contribution | 3 days on-site coating trials using commercial pilot scale fluidised bed coaters were provided free of charge (incl. materials) supported by senior scientists. |
Impact | Internal report on the feasibility of the OCT sensor has been characterised where we were able to resolve film coatings. |
Start Year | 2019 |
Description | Johnson Matthey Fuel Cell Materials |
Organisation | Johnson Matthey |
Department | Johnson Matthey Technology Centre |
Country | United Kingdom |
Sector | Private |
PI Contribution | Fuel cell materials characterisation and analysis |
Collaborator Contribution | Materials exchange |
Impact | Scientific reports have been produced. |
Start Year | 2019 |
Description | 2020 Invited Keynote at UK-Russia Bioinspired materials conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | An interdisciplinary conference bringing together researchers from all aspects of biomaterials research, which sparked questions, discussions and collaborations thereafter. |
Year(s) Of Engagement Activity | 2020 |
Description | Academic conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The research talk initiated discussion on the technique presented from the industry and general academic audience. |
Year(s) Of Engagement Activity | 2020 |
Description | Academic conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The research talk initiated discussion on the technique presented from the industry and general academic audience. |
Year(s) Of Engagement Activity | 2020 |
Description | Invited talk and panel discussion at H2FC Supergen |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Brought out an awareness on the possibility of the technology resulting in further discussions with practitioners at NPL, Imperial College and Manchester Fuel Cell Innovaton Center. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.h2fcsupergen.com/clean-energy/moving-ahead-with-hydrogen-review/ |
Description | Presentation at academic conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The research talk initiated discussion on the technique presented from the industry and general academic audience. |
Year(s) Of Engagement Activity | 2020 |
Description | Research presentation on fuel cell quality control |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Research presentation on sparked interests and discussions on future collaborations |
Year(s) Of Engagement Activity | 2020 |
URL | http://www.h2fcsupergen.com/hydrogen-research-conference-2020/ |
Description | Research presentation on terahertz data processing and fuel cell quality control |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The research talk initiated discussion on the technique presented from the industry and general academic audience. |
Year(s) Of Engagement Activity | 2019 |
URL | http://www.irmmw-thz2019.org/ |
Description | Research showcase on optical sensing application in pharmaceutical manufacturing |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Research presentation on sparked interests and discussions on future collaborations |
Year(s) Of Engagement Activity | 2020 |
URL | https://ktn-uk.co.uk/events/analytical-challenges-solutions-for-medicines-manufacturing-towards-indu... |
Description | Talk at Johnson Matthey |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Discussions on technology limitations and opportunities for collaborations via PhD studentships. |
Year(s) Of Engagement Activity | 2022 |