Application of Raman spectroscopy for on-line monitoring of low dose blend uniformity.
On-line Raman spectroscopy was used to evaluate the effect of blending time on low dose, 1%, blend uniformity of azimilide dihydrochloride. An 8 qt blender was used for the experiments and instrumented with a Raman probe through the I-bar port. The blender was slowed to 6.75 rpm to better illustrate the blending process (normal speed is 25 rpm). Uniformity was reached after 20 min of blending at 6.75 rpm (135 revolutions or 5.4 min at 25 rpm). On-line Raman analysis of blend uniformity provided more benefits than traditional thief sampling and off-line analysis. On-line Raman spectroscopy enabled generating data rich blend profiles, due to the ability to collect a large number of samples during the blending process (sampling every 20s). In addition, the Raman blend profile was rapidly generated, compared to the lengthy time to complete a blend profile with thief sampling and off-line analysis. The on-line Raman blend uniformity results were also significantly correlated (p-value < 0.05) to the HPLC uniformity results of thief samples.
Hausman
Debra S
DS
Industrial Pharmacy Graduate Program, College of Pharmacy, University of Cincinnati, 3223 Eden Avenue, Cincinnati, OH 45267, USA. hausman.ds@pg.com
Cambron
R Thomas
RT
Sakr
Adel
A
D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D006827:Hydantoins; D048289:Imidazolidines / Q000008:administration & dosage* / Q000737:chemistry*; D010879:Piperazines / Q000008:administration & dosage* / Q000737:chemistry*; D013059:Spectrum Analysis, Raman; D013678:Technology, Pharmaceutical
D006827:Hydantoins; D048289:Imidazolidines; D010879:Piperazines; C086123:azimilide