The Roadmap To Your Next Crystallization. Awww, not P-Chem again !!

     I came across this article in Organic Process Research & Development and thought I might discuss it.  I can see the value in being able to come up with a phase diagram for the API system you are working on.  There was one crystallization procedure, that I had worked on, where my project team really wanted to get the product in one crystal form.  I, also, remember an eager colleague, who decided to reverse the order of my protocol and ended up with another polymorph.  The phase diagram is, in essence, a roadmap for your crystallization.  It would supply you with the right conditions to attain your desired crystal form, and what conditions to avoid that would give a different crystal form.

     When I saw the following paper by Terence Threlfall, “Turning DSC Charts of Polymorphs into Phase Diagrams:A Tutorial Paper”, Organic Process Research and Development, 2009, 13, p. 1224-30, I was intrigued.  I don’t think I have come across a tutorial paper in OPRD before.  I found out it wasn’t as easy as it seems.  The title made me think it was deceptively simple, but upon reading the article, it does not seem straightforward.  The author mentions that the DSC traces, along with reslurry experiments and solubility measurements, can help you put together a crude phase diagram.  The understanding of the polymorphic system and its behaviour can be better understood through the use of such a phase diagram.  Rather than try and summarize the paper, I hope I have summarized enough of it, that you might be curious and take a look.

     I am always looking for those enhanced-value experiments that given the know-how, would provide a lot of data that could save time and money (dare I say that).  It would seem that the materials needed to carry out such a study would be minimal.  Not fully understanding a crystallization and the parameters needed to control a crystal form can slow down every aspect of the project, from producing clinical material for clinical trials to formulation issues.

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