In 2013, Medichem decided to integrate a Flow Chemistry process line to its Spanish plant, located in Celrà (Girona). By this continuous processing line, Medichem wants to consolidate its presence in the generic pharmaceutical industry and offer to its customers more advantages of flow over traditional batch and semi-batch processing.
WHAT IS THE FLOW CHEMISTRY?
In the pharma and specialty chemicals, Organic synthesis is generally conducted in a batch mode. In the last decades, the interest in Flow Chemistry has increased due to the economic and environmental pressures and promotion from regulatory authorities such as FDA. It is no longer in its infancy, and has been widely studied by the chemical industry for many years.
However, implementation of continuous processes in pharmaceutical manufacturing is not a standard practice.
Currently, Medichem offers this technology in its Spanish Plant (Celrà, Girona). However, since the equipment is mobile, this technology can also be offered from our Malta plant to benefit also from the IP situation there.
In a continuous flow system the chemical reaction is carried out with a continuous supply of starting materials. In other words, the reactants are pumped into a microreactor and they start reacting as soon as they mix.
BENEFITS OF FLOW CHEMISTRY?
Chemistry in flow provides exquisite control over reaction conditions:
BETTER HEAT TRANSFER EFFICIENCY Reactions which are largely exothermic can be carried out without thermal risk in flow as the energy produced is removed more efficiently than in batch mode.
SUPERIOR MIXING QUALITY: In batch, mixing is promoted by stirrers or agitators. In flow mixing occurs by diffusion only and the speed with which homogeneous reaction mixtures are obtained is significantly increased.
SCALE-UP ISSUES ARE MINIMIZED: Transference from laboratory scale to production sites can be carried out without the need for reoptimization / redesign of the synthetic process. Uniform reaction conditions are obtained meaning that each molecule in flow experience the same reaction times, temperatures and pressures.
IMPROVED REACTION SELECTIVITY: Conditions in flow can be fine tuned to avoid or minimize side-reactions more efficiently than in the batch strategy.
FASTER REACTIONS: The flow strategy opens the window to work under pressure, at temperatures above the solvent boiling point. This issue together with the better mixing efficiency allows speeding up reactions significantly. Generally speaking, a flow reaction takes from seconds to few minutes.
IMPROVED SAFETY BY LOWER INTERNAL VOLUME: Flow reactors offers many advantages including improved safety due to their low hold-up volume allowing only a small amount of hazardous intermediate to be formed instantaneously and avoiding inventory of unstable intermediates in case of multistep reaction. Their high surface area also allows excellent control of exothermic reactions, resulting in safer process.
FLOW CHEMISTRY ALSO ALLOWS:
RAPID REACTION OPTIMIZATION: The performance of a Design of Experiments (DoE) using flow is easier and much faster. The stoichiometry is changed by only modifying the flow rates of the reactants.
PERFORMING DANGEROUS CHEMISTRY: Hazardous chemicals are present in small amounts inside the channels. In addition, the efficient heat transfer allows performing very exothermic reactions without thermal risk.
REACTIONS UNDER PRESSURE: Temperatures above the boiling point of the solvent can be easily reached in flow by pressurizing the system. In this way very fast reactions can be designed and the use of gaseous reactants becomes easier.
CRYOGENIC REACTIONS, LOW TEMPERATURE CHEMISTRY: Carrying out reactions at very low temperatures in batch is not trivial while it is easy to handle this kind of chemistry in flow.
Medichem can provide scale up services from R&D to industrial scale.
THE LAB SETTING INCLUDES:
- Fully automated dosing lines
- Heating and cooling capacity
- Lab-scale microreactors in glass and stainless steel
THE INDUSTRIAL SETTING INCLUDES:
- 3 fully automated pumping units from 0 bar to 20 bar
- 1 industrial G4 Corning reactor. up to 300 Kg/h processed
- Heating and cooling capacity from +200ºC to -60ºC