The Modern Synthesis Lab
This white paper outlines the pressures driving change, the limitations of traditional synthesis workflows, a practical modernization framework, and where EasyMax 102i can support the journey.
Our processes have of course to be economically viable. And you can imagine that with a chemical synthesis with 30 steps or more, the yield of each step has to be above 95%. This is a very good reason to use design of experiment for process development. In the new quality by design approach, It is expected that the relationship between process parameters and product quality is clearly established. Design of experiment is widely applied across industry. In this talk, Didier Monnaie from Lonza outlines why precision is imperative to conducting a successful DOE. It is very important to control all parameters as tightly as possible. If the process parameters are not in control, It will translate into noisy responses and the power of the DOE analysis will be decreased. Factor effects will not stand out of the noise of the system. So how do you precisely record and control dosing, temperature, pH and all the other parameters needed to complete a full factorial set without slowing development time? Lanza opted for an established automated synthesis reactor to increase productivity. We used the EasyMax equipment. The mechanical stirring system with an impeller allows for a good and reproducible mixing. It has an accurate dosage system that was used to deliver the trifluoroacetic acid. It has an accurate and precise temperature control system. Moreover, the handling of the equipment is made easy. Some operations like dosage, temperature settings, stirring are automated. It has been possible for technicians to run several reactions in parallel. Otherwise, we cannot get reliable mathematical models for the reaction. The automated setup allowed Monnaie and his team to quickly collect accurate data and build mathematical models to identify parameters for process and product optimization. Our experience has shown that the use of design of experiment has improved our process understanding. On the basis of the two mathematical models, it is then possible to identify the best conditions for the reaction. The best reaction conditions were rapidly identified, much more rapidly than in the traditional approach. Learn more about accelerating your design of experiment. Download the free white paper at mt.com slash wp-doe.
Design of Experiment studies facilitate fast and efficient discovery and development of new chemical entities, which was an ongoing challenge. Organic chemists and engineers apply various techniques and methods to improve synthetic pathways, so that they become more effective and minimize the consumption of precious starting material. Advancements in synthesis methods and tools have made improvements possible.
In synthetic organic chemistry labs, obstacles or constraints still surface and need to be resolved. A chemical reaction is affected by multiple parameters, making it difficult to find optimal parameters quickly and efficiently. Chemistry can be influenced by parameters including concentration, addition rate, temperature, the solvent, catalyst and pH. Frequently, parameters influence each other. Reactions may also be affected by the stirrer type and speed, which impact the mass transfer and further influence the result of the experiment.
Rather than adopting a "trial-and-error" approach, where each parameter is examined individually and interactions between them cannot easily be detected, scientists can apply the Design of Experiments (DoE) methodology in the synthetic organic chemistry lab. A white paper describes the DoE approach and how it is used to identify the relationship between parameters, defining optimal settings at which the response variable (including yield, selectivity, impurity level) reaches the ideal value.
Two Design of Experiment (DoE) case studies are presented:
- Researchers at the Zurich University of Applied Sciences (ZHAW) investigated styrene polymerization to:
- Understand the performance and accuracy of temperature control, a pre-requisite for reliable Design of Experiment (DoE) studies
- Track progress and repeatability
- Scientists at Lonza SA explored a Peptide Synthesis reaction to:
- Identify the impact of reaction parameters
- Provide a better understanding of the cause and effect of process variability
- Shorten chemical development cycles
- Support the Quality-by-Design (QbD) approach
More Design of Experiments (DoE) Resources
DoE to Peptide Synthesis
Learn how Design of Experiments (DoE) is applied to chemical synthesis at Lonza Peptide.
Techniques to Synthesize Breakthrough Molecules
Advances in organic chemistry allow researchers to expand R&D of molecules and optimize process conditions. A new white paper presents 4 case studies where pharma companies implement new synthesis techniques.
Design of Experiments (DoE) Studies
Design of Experiments (DoE) requires experiments to be conducted under well-controlled and reproducible conditions in chemical process optimization. Chemical synthesis reactors are designed to perform DoE investigations ensuring high quality data.
