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Topic: Adapt Czochralski to Chiral Separation  (Read 11030 times)

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Offline discodermolide

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Re: Adapt Czochralski to Chiral Separation
« Reply #15 on: February 13, 2013, 01:44:36 PM »
Here is a typical problem in the Pharma business. This an abstract from Organic Process Research & Development, 2013, by Dufour etal, Title "Control of Crystal Modification and Crystal Shape by Control of Solid−Solid Transitions during Crystallization and Drying: Two Industrial Case Studies" doi.org/10.1021/op300333h

"Crystallization and drying are the final steps in the manufacture of most drug substances that determine their final features and may also impact the manufacture of the formulated drug product. It is important to understand and control the mechanisms involved in the crystallization and drying processes to avoid handling and formulation problems, and this is illustrated with two examples of large-scale processes. In the first, a solid−solid phase transition between two very similar crystalline forms was shown to lead to dramatic particle size reduction and consequent processing issues; the unwanted phase transition was avoided by careful choice of crystallization conditions. In the second, control of the drying conditions allowed a rapid solid−solid phase transition of a mixed solvate into a stable anhydrous form."

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Offline Enthalpy

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Re: Adapt Czochralski to Chiral Separation
« Reply #16 on: February 13, 2013, 06:46:57 PM »
...a new crystal form of aspirin was claimed, after years of having stable polymorphs.
Fun.

Well, they still discover new forms of (water) ice, despite ice has been known for quite a few years. The new ones appear under extreme pressure, cheating, OK.

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The answer against polymorphs must be to impose how the melt or solution is to crystallize, and this is what Czochralski improves, as is tunes to melting or dissolving conditions (temperature, concentration) through all the liquid except the small zone where the desired crystal form is already present.

It's, as I believe to understand it, what lets grow single crystals of silicon, because seeds don't form elsewhere as conditions are melting instead of freezing. The same reason must prevent seeds of organic "heteromorphs" to appear, and the liquid or solute must aggregate only to the existing solid as the conditions permit it only there, and then follow the available crystal form.

Offline discodermolide

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Re: Adapt Czochralski to Chiral Separation
« Reply #17 on: February 13, 2013, 10:13:45 PM »
No answer to that!
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