omation mbers - Society for Laboratory Automation and Screening
omation mbers - Society for Laboratory Automation and Screening
omation mbers - Society for Laboratory Automation and Screening
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2:00 pm Thursday, February 5 Aut<strong>omation</strong> Applications in Process R&D Room A2<br />
Kara Rubin<br />
Merck Research Laboratories<br />
RY800-C210 P.O. Box 2000<br />
Rahway, New Jersey 08859<br />
Kara_Rubin@Merck.com<br />
Accelerating Polymorph <strong>and</strong> Salt Form Selection<br />
Crystallization of active pharmaceutical ingredients <strong>and</strong> their key intermediates has played an important role<br />
<strong>for</strong> pharmaceutical companies in getting a drug to market. Within Merck’s Process Research department<br />
crystallizations have been used in organic synthesis <strong>for</strong> various reasons, including the enhancement of chemical<br />
stability, resolution of enanitomers <strong>and</strong> purification. To accelerate this phase of the drug compound development<br />
process Merck entered into collaboration with Symyx Technologies to develop a High Throughput Polymorph<br />
<strong>and</strong> Salt <strong>Screening</strong> workflow. In this workflow, polymorph screens are per<strong>for</strong>med to determine possible phase<br />
compositions, which are crystallized from various solvent combinations using a variety of procedures. Salt screens<br />
are per<strong>for</strong>med on active drug molecules in the presence of various pharmaceutically acceptable bases or acids.<br />
The solids produced by the screens can be automatically analyzed by polarized light microscopy, X-ray powder<br />
diffraction, Raman spectroscopy, <strong>and</strong> melting point determination.<br />
2:30 pm Thursday, February 5 Aut<strong>omation</strong> Applications in Process R&D Room A2<br />
Brent Karcher<br />
Bristol-Myers Squibb Co.<br />
One Squibb Drive<br />
P.O. Box 0191<br />
New Brunswick, New Jersey 08903<br />
brent.karcher@bms.com<br />
MeDuSA, An Automated HPLC <strong>Screening</strong> Tool For PR&D<br />
94<br />
Co-Author(s)<br />
Merrill L. Davies<br />
Jack Venit<br />
Edward Delaney<br />
An automated tool <strong>for</strong> HPLC has been designed which enables process scientists to critically challenge currently<br />
utilized <strong>and</strong>/or accepted HPLC methods of analysis. Samples are subjected to a rigorous HPLC gauntlet<br />
comprised of an array of analytical reversed-phase columns possessing different selectivities, gradient elution<br />
using different eluents of various pH <strong>and</strong> solvent blends, with dual wavelength absorption detection. The resulting<br />
absorption data are presented as stacked chromatograms to provide a comprehensive picture of a sample’s<br />
impurity profile <strong>and</strong> a quick assessment of the best conditions to achieve chromatographic resolution of all<br />
sample components. The HPLC conditions are also amenable to both evaporative light scattering (ELS) <strong>and</strong> mass<br />
spectrometric (MS) detection. The entire package is controlled by custom software which streamlines sample<br />
queuing <strong>and</strong> HPLC control to af<strong>for</strong>d a user-friendly “walk-up” system. The multi-dimensional screening <strong>and</strong><br />
analysis (MeDuSA) concept has also been successfully extended to both reversed-phase chiral <strong>and</strong> normal-phase<br />
chiral HPLC. In addition, a mini-MeDuSA, utilizing shorter (50 mm) columns <strong>and</strong> higher flow rates, was developed<br />
to provide the analytics needed to support parallel experiments <strong>and</strong> high throughput screening.
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