Pharmaceutical scale up

During the development of a new medicine, the chemistry involved may need to be scaled up several times. From bench top to test scale to batches and large-scale reactors; the chemistry and chemicals used in a specific reaction may need to be tweaked to suit the suit the scale of the reaction.

There are many factors that need to be considered during pharmaceutical scale up, including some of the following:

Exotherm control

Grignard reagents - and the ether solvents used to prepare them - are highly flammable. Scaling up requires precise control of exothermic reactions to minimize the risk of fire or explosion.

Reactor conditions

Efficient mixing is important to ensure a controlled reaction and to prevent hot spots. Slow reagent addition of and controlled reaction initiation is important in pyrophoric reactions like the Grignard reaction.

Purification

Scaling up your reaction includes scaling up purification! Optimize your reaction to minimize by-products and allow for simple purification - or none if the reaction is highly selective.

Reaction design

Scaling from bench to chemical plant often means adapting the process all the way from charging the reaction vessel with starting materials to isolating the pure product. What works on one scale may not be the best approach for another.