Biotage metal scavengers are widely proven and adopted solutions for the removal of metals such as palladium, from chemical products such as APIs and used in industry thousands of times, the world over for over 20 years. However, there are other (inferior to our ears) metal scavengers that have been put onto the market by others that have confused, given inconsistent results and weakened process robustness in pharmaceutical applications.
Another excellent question we received following seminars and presentations relates to the function and activity of metal scavengers. IUPAC nomenclature rules combined with various naming systems and also a chemists appetite for simple readily identifiable reagents, has led to a rather unfortunate conclusion, that to the uninitiated, metal scavengers can seem all the same.
It’s engrained in our minds and psyche, from earliest school days and exposures to science that heating a reaction speeds it up. Later, we learn some more of the details, that by increasing the temperature of a reaction, we can double its reaction rate. And after, the Arrhenius equation (Figure 1) is revealed to us, completing the picture and making the science infallible.
Once a chemist has seen and understands potential for the application of metal scavenging and reduction of classical iterative metal migration steps, the next question I usually receive, relates to how best to apply them to a reaction.
In this blog, I will address something that is fundamental to years of classic process chemistry techniques. First disclaimer is that the pharma industry uses recrystallization for several purposes, nearly always for the creation of purer product and sometimes in connection with isolation of specific crystalline forms.
After my seminars, I often receive questions from astute attendees on the topic of activated carbon, and how the more modern powerful approach of metal scavenging compares to the traditional application of activated carbon. This can be an emotive topic, sometimes the question can be a blunt as ‘What’s wrong with carbon? It’s the way most process groups have historically removed transition metals such as palladium.'
Once a chemist has seen and understands potential for the application of metal scavenging and reduction of classical iterative metal migration steps, the next question we receive usually relates to how best to apply them to a reaction.
Removing palladium has become more and more difficult for a number of reasons. Industry is using it more frequently, due to its greener credentials as a catalyst but regulatory bodies are also reducing acceptable limits in APIs. One of the most significant changes for pharma recently has been increased scrutiny of impurities in pharma products.
There are two starting points, depending on your preference of whether you want to stir in a batch or flow something though a tube. If you plan to use large scale up reactors, then batch stir methods are great, but if you imagine wanting to flow material through a ‘cleaning’ column, then the SPE quick test works well.
Now we have a screening candidate, we just need to scale up our work, it is always advisable to initially to scale in factors of ~10 in our experience, although for well-used processes and repetitive batch processing, it is possible to screen grams and go straight to Kgs.