TY - JOUR

T1 - Comparison of torque measurements and near-infrared spectroscopy in characterization of a wet granulation process

AU - Jørgensen, Anna Cecilia

AU - Luukkonen, Pirjo

AU - Rantanen, Jukka

AU - Schaefer, Torben

AU - Juppo, Anne Mari

AU - Yliruusi, Jouko

PY - 2004/9

Y1 - 2004/9

N2 - The purpose of this study was to compare impeller torque measurements and near-infrared (NIR) spectroscopy in the characterization of the water addition phase of a wet granulation process. Additionally, the effect of hydrate formation during granulation on the impeller torque was investigated. Anhydrous theophylline, alpha-lactose monohydrate, and microcrystalline cellulose (MCC) were used as materials for the study. The materials and mixtures of them were granulated using purified water in a small-scale high-shear mixer. The impeller torque was registered and NIR spectra of wet samples were recorded at-line. The torque and the NIR baseline-corrected water absorbances increased with increasing water content. A plateau in the NIR baseline-corrected water absorbances was observed for wet masses containing MCC. This was at the region of optimal water amount for granulation according to the torque results. In the case of anhydrous theophylline, the slope of baseline-corrected water absorbance values increased at the same water amount as the impeller torque started to increase. The hydrate formation of theophylline during granulation was observed as a slight decrease in the impeller torque. In addition, the hydrate formation during granulation affected the granulation liquid requirement. The liquid requirement was different for monohydrate formed during granulation compared to one formed in high relative humidity before the granulation. The results suggest that NIR spectroscopy may be applicable to process monitoring of wet granulation, also in cases where monitoring of impeller torque is difficult to apply.

AB - The purpose of this study was to compare impeller torque measurements and near-infrared (NIR) spectroscopy in the characterization of the water addition phase of a wet granulation process. Additionally, the effect of hydrate formation during granulation on the impeller torque was investigated. Anhydrous theophylline, alpha-lactose monohydrate, and microcrystalline cellulose (MCC) were used as materials for the study. The materials and mixtures of them were granulated using purified water in a small-scale high-shear mixer. The impeller torque was registered and NIR spectra of wet samples were recorded at-line. The torque and the NIR baseline-corrected water absorbances increased with increasing water content. A plateau in the NIR baseline-corrected water absorbances was observed for wet masses containing MCC. This was at the region of optimal water amount for granulation according to the torque results. In the case of anhydrous theophylline, the slope of baseline-corrected water absorbance values increased at the same water amount as the impeller torque started to increase. The hydrate formation of theophylline during granulation was observed as a slight decrease in the impeller torque. In addition, the hydrate formation during granulation affected the granulation liquid requirement. The liquid requirement was different for monohydrate formed during granulation compared to one formed in high relative humidity before the granulation. The results suggest that NIR spectroscopy may be applicable to process monitoring of wet granulation, also in cases where monitoring of impeller torque is difficult to apply.

KW - Spectroscopy, Near-Infrared

KW - Technology, Pharmaceutical

KW - Torque

U2 - 10.1002/jps.20132

DO - 10.1002/jps.20132

M3 - Journal article

C2 - 15295784

VL - 93

SP - 2232

EP - 2243

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 9

ER -