327815 A Model for Crystal Growth for Solids Crystallizing From Solutions Containing Multiple Conformers and Evidence of Growth Inhibition By the “Wrong Conformer”

Wednesday, November 6, 2013: 1:10 PM
Union Square 1 (Hilton)
Lotfi Derdour, Drug Product Science and Technology, Bristol-Myers Squibb co., New Brunswick, NJ, Chandrasekar Sivakumar, Chemical Engineering, Carnegie Mellon University, Pittsburg, PA, Dimitri Skliar, Chemical Development, Bristol-Myers Squibb, New Brunswick, NJ, Shawn Pack, Chemical Development, Bristol-Myers Squibb Co., New Brunswick, NJ, Chiajen Lai, Drug Product Science and Technology, Research and Development, Bristol-Myers Squibb Company, New Brunswick, NJ, James Vernille, Chemical Development, Bristol Myers Squibb, New Brunswick, NJ and San Kiang, Bristol-Myers Squibb Company, New Brunswick, NJ

The validity of a model derived for crystal growth rate for solids crystallized from solutions containing multiple conformers is evaluated. A simple and straightforward method for determining crystal growth rates using FBRM and FTIR/ATR is utilized to maximize growth rate data collected from a single experiment. Crystal growth rate data obtained experimentally were in good agreement with model predictions. In particular, the data indicated that when the approach of the right conformer (Derdour et al. Chem Eng Sci., 66(1), pp. 88-102, 2011) applies, crystal growth rate is inversely proportional to crystal size. Further, the results indicate that growth rates determined from supersaturation measurements can be over-estimated because of surface nucleation and/or agglomeration that can result from supersaturation spikes during anti-solvent addition. Lastly, crystal growth data obtained at different temperatures indicated that the slow growth rate observed at low temperatures may be caused in part by surface poisoning by the wrong conformer.

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