On-line application of near-infrared spectroscopy for monitoring water levels in parts per million in a manufacturing-scale distillation process.
An on-line analytical method based on transmission near-infrared spectroscopy (NIRS) for the quantitative determination of water concentrations (in parts per million) was developed and applied to the manufacture of a pharmaceutical intermediate. Calibration models for water analysis, built at the development site and applied at the manufacturing site, were successfully demonstrated during six manufacturing runs at a 250-gallon scale. The water measurements will be used as a forward-processing control point following distillation of a toluene product solution prior to use in a Grignard reaction. The most significant impact of using this NIRS-based process analytical technology (PAT) to replace off-line measurements is the significant reduction in the risk of operator exposure through the elimination of sampling of a severely lachrymatory and mutagenic compound. The work described in this report illustrates the development effort from proof-of-concept phase to manufacturing implementation.
Eli Lilly and Company, SMDD, Indianapolis, IN 46285 USA.
Gordon
G
Lambertus
Zhenqi
Z
Shi
Robert
R
Forbes
Timothy T
TT
Kramer
Steven
S
Doherty
James
J
Hermiller
Norma
N
Scully
Sze Wing
SW
Wong
Mark
M
LaPack
D057168:Distillation / Q000295:instrumentation / Q000379:methods*; D019265:Spectroscopy, Near-Infrared / Q000295:instrumentation / Q000379:methods*; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D014867:Water / Q000032:analysis* / Q000737:chemistry
D014867:Water