TY - JOUR

T1 - Monitoring the film coating unit operation and predicting drug dissolution using terahertz pulsed imaging

AU - Ho, Louise

AU - Müller, Ronny

AU - Gordon, Keith C

AU - Kleinebudde, Peter

AU - Pepper, Michael

AU - Rades, Thomas

AU - Shen, Yaochun

AU - Taday, Philip F

AU - Zeitler, J Axel

N1 - 2009 Wiley-Liss, Inc. and the American Pharmacists Association

PY - 2009

Y1 - 2009

N2 - Understanding the coating unit operation is imperative to improve product quality and reduce output risks for coated solid dosage forms. Three batches of sustained-release tablets coated with the same process parameters (pan speed, spray rate, etc.) were subjected to terahertz pulsed imaging (TPI) analysis followed by dissolution testing. Mean dissolution times (MDT) from conventional dissolution testing were correlated with terahertz waveforms, which yielded a multivariate, partial least squares regression (PLS) model with an R(2) of 0.92 for the calibration set and 0.91 for the validation set. This two-component, PLS model was built from batch I that was coated in the same environmental conditions (air temperature, humidity, etc.) to that of batch II but at different environmental conditions from batch III. The MDTs of batch II was predicted in a nondestructive manner with the developed PLS model and the accuracy of the predicted values were subsequently validated with conventional dissolution testing and found to be in good agreement. The terahertz PLS model was also shown to be sensitive to changes in the coating conditions, successfully identifying the larger coating variability in batch III. In this study, we demonstrated that TPI in conjunction with PLS analysis could be employed to assist with film coating process understanding and provide predictions on drug dissolution.

AB - Understanding the coating unit operation is imperative to improve product quality and reduce output risks for coated solid dosage forms. Three batches of sustained-release tablets coated with the same process parameters (pan speed, spray rate, etc.) were subjected to terahertz pulsed imaging (TPI) analysis followed by dissolution testing. Mean dissolution times (MDT) from conventional dissolution testing were correlated with terahertz waveforms, which yielded a multivariate, partial least squares regression (PLS) model with an R(2) of 0.92 for the calibration set and 0.91 for the validation set. This two-component, PLS model was built from batch I that was coated in the same environmental conditions (air temperature, humidity, etc.) to that of batch II but at different environmental conditions from batch III. The MDTs of batch II was predicted in a nondestructive manner with the developed PLS model and the accuracy of the predicted values were subsequently validated with conventional dissolution testing and found to be in good agreement. The terahertz PLS model was also shown to be sensitive to changes in the coating conditions, successfully identifying the larger coating variability in batch III. In this study, we demonstrated that TPI in conjunction with PLS analysis could be employed to assist with film coating process understanding and provide predictions on drug dissolution.

U2 - 10.1002/jps.21766

DO - 10.1002/jps.21766

M3 - Journal article

C2 - 19367620

VL - 98

SP - 4866

EP - 4876

JO - Al Azhar Journal of Pharmaceutical Sciences

JF - Al Azhar Journal of Pharmaceutical Sciences

SN - 1110-1644

IS - 12

ER -