In-line monitoring of a pharmaceutical blending process using FT-Raman spectroscopy.
FT-Raman spectroscopy (in combination with a fibre optic probe) was evaluated as an in-line tool to monitor a blending process of diltiazem hydrochloride pellets and paraffinic wax beads. The mean square of differences (MSD) between two consecutive spectra was used to identify the time required to obtain a homogeneous mixture. A traditional end-sampling thief probe was used to collect samples, followed by HPLC analysis to verify the Raman data. Large variations were seen in the FT-Raman spectra logged during the initial minutes of the blending process using a binary mixture (ratio: 50/50, w/w) of diltiazem pellets and paraffinic wax beads (particle size: 800-1200 microm). The MSD-profiles showed that a homogeneous mixture was obtained after about 15 min blending. HPLC analysis confirmed these observations. The Raman data showed that the mixing kinetics depended on the particle size of the material and on the mixing speed. The results of this study proved that FT-Raman spectroscopy can be successfully implemented as an in-line monitoring tool for blending processes.
Vergote
G J
GJ
Faculty of Pharmaceutical Sciences, Laboratory of Pharmaceutical Technology, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium.
De Beer
T R M
TR
Vervaet
C
C
Remon
J P
JP
Baeyens
W R G
WR
Diericx
N
N
Verpoort
F
F
D005583:Fourier Analysis; D013059:Spectrum Analysis, Raman / Q000379:methods*; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*