“In Silico Techniques” at the Joint Pharmaceutical Analysis Group Meeting

Back To Discover

Written by

Andrew Maloney

Posted on

February 18, 2020

I always like visiting the headquarters of the Royal Society of Chemistry at Burlington House. Situated on London’s Piccadilly, it shares a courtyard with the Royal Academy as well as four other “learned societies”. It’s an impressive building, and inside there is a great sense of scientific heritage, from the multitude of books that line the walls to the portraits of eminent chemists gazing down. It was here that I found myself on the 6th of February for an “In Silico Techniques” meeting of the Joint Pharmaceutical Analysis Group (JPAG).

JPAG is a not-for-profit organisation “run for pharmaceutical analysts by pharmaceutical analysts”, and has been serving its members for 50 years, making it almost as venerable as the CCDC. JPAG hold regular meetings to share best practice and advice among the pharmaceutical community, and I was fortunate to have been invited to give a presentation on “Digital Design” to start the day.

I set out to describe ways that the Cambridge Structural Database (CSD) can be used to understand the links between structural features and potential development and formulation issues in the pharmaceutical industry. The knowledge in the CSD can be used to understand a drug from the molecule to the solid form and beyond, and how structural information can provide insights into the mechanical and physical properties of a substance. I talked about how, by recognising patterns of intermolecular interactions that occur again and again in over one million structures in the CSD, we can answer questions about polymorphic stability and how we might design novel multi-component systems such as co-crystals. Lots of questions followed the presentation, including one about how adding more structures to the CSD affects the conclusions we can draw from our analyses. The statistical power of the CSD improves with each new entry, and so it becomes more and more useful as the number of structures increases.



The next presentation was by Edd Close from Process Systems Enterprise (PSE). Edd talked about Systems-based Pharmaceutics, with a focus on modelling dissolution and stability during drug product performance. We have started to collaborate with PSE on several projects in the last few years, and so it’s always interesting to hear their perspective on the way new advancements come together to make pharmaceutical manufacturing more efficient.

Edd was followed by Patrick Wray from Bristol-Myers Squibb who talked about the importance of automating data processing to rapidly assess the results of stability studies. Having robust processes in place to handle large amounts of data is not only crucial to identifying and understanding changes in form, it can also be invaluable to facilitate quantitative model development based on this data. Knowing that the data being analysed can be relied on is critical to the pharmaceutical industry. The morning session was rounded off by presentations from Lhasa Ltd. and ACD/Labs, who talked about recent developments in physicochemical property prediction.

Over lunch I chatted to several other delegates including David Elder, the current Chairman of JPAG. David was very interested in the diversity of pharmaceutical salts in the CSD, and has promised to bring in his thesis to the CCDC so that we can enter the crystal structures that he generated during his PhD studies over thirty years ago into the database. It’s never too late to submit a structure!

Garry Scrivens from Pfizer started the afternoon session with a very interesting presentation on the stability of solid dosage forms in terms of the composition of the formulation and the particle size. Garry talked about the many different factors that can lead to degradation, and it was fascinating to hear about this from a structural perspective. These kinds of questions are the sort that we’ve been trying to answer through projects like ADDoPT (Advanced Digital Design of Pharmaceutical Therapeutics), and being able to share both scientific knowledge and experimental data from case studies with industrial partners is key to making progress in our ability to understand and predict when problems relating to pharmaceutical stability will arise.

Next, Mel Euerby from Shimadzu described his experiences in modelling and optimisation for chromatography method development, before James Mann from AstraZeneca told us about the DUST (Dissolution Universal Strategy Tool). This is an approach that encourages scientists to look after their dissolution data in order to make sure that they have a robust control strategy. The DUST was developed with years of experience with pharmaceutical regulators in mind, again demonstrating the importance of having carefully structured data and the benefits to understanding the pharmaceutical development process that this brings.

The day over, it was time to leave this historic setting and set out into the streets of London on a cold February evening. The JPAG meeting was an excellent experience; I enjoyed sharing knowledge and experiences with a diverse community of pharmaceutical scientist and I learned a lot of new things to bring back to the CCDC. I’m certainly looking forward to the next one!