Hiroshi Uchida1, Makoto Otsuka. 1. Kyorin Pharmaceutical Co. Ltd, Tochigi, and Research Institute of Pharmaceutical Science, Musashino University, Nishi-Tokyo, Japan.
Abstract
OBJECTIVES: This study was conducted to test whether our novel combination (i.e. microanalysis) of near-infrared (NIR) spectroscopy and humidity-controlled 96-well plate, reported in a previous issue of this journal, can be successfully applied to quantitative evaluation of the pseudopolymorphic transformation of imidafenacin. METHODS: Sample powders of a drug compound were placed in a humidity-controlled 96-well plate containing various saturated salt solutions, and stored at 35°C. NIR spectra were collected using a Fourier transform-NIR spectrometer in combination with a fiber-optic probe. The actual hydrate contents of samples were determined by using thermal gravimetric analysis (TGA). A series of sets of NIR spectra and TGA data were used to establish a calibration model with which to predict the contents of monohydrate by partial least-squares regression (PLS). KEY FINDINGS: The PLS calibration model analysis showed that the plots of NIR predicted values to the actual values gave a straight line with correlation coefficients of 0.9868 and 0.9936, respectively, for the 96-well plate and glass-bottle uses. The model using the 96-well plate was therefore able to predict the transformation of imidafenacin in one form to another form as quantitatively as the conventional model using glass bottles. CONCLUSION: The present study confirmed that our microanalysis quantitatively predicts the pseudopolymorphic transformation of our tested drug in small amounts and suggests that this particular method is a simple and convenient one that may be efficiently applied to polymorphic and pseudopolymorphic studies of a hygroscopic drug candidate, at even earlier development stages than the conventional method using glass bottles.
OBJECTIVES: This study was conducted to test whether our novel combination (i.e. microanalysis) of near-infrared (NIR) spectroscopy and humidity-controlled 96-well plate, reported in a previous issue of this journal, can be successfully applied to quantitative evaluation of the pseudopolymorphic transformation of imidafenacin. METHODS: Sample powders of a drug compound were placed in a humidity-controlled 96-well plate containing various saturated salt solutions, and stored at 35°C. NIR spectra were collected using a Fourier transform-NIR spectrometer in combination with a fiber-optic probe. The actual hydrate contents of samples were determined by using thermal gravimetric analysis (TGA). A series of sets of NIR spectra and TGA data were used to establish a calibration model with which to predict the contents of monohydrate by partial least-squares regression (PLS). KEY FINDINGS: The PLS calibration model analysis showed that the plots of NIR predicted values to the actual values gave a straight line with correlation coefficients of 0.9868 and 0.9936, respectively, for the 96-well plate and glass-bottle uses. The model using the 96-well plate was therefore able to predict the transformation of imidafenacin in one form to another form as quantitatively as the conventional model using glass bottles. CONCLUSION: The present study confirmed that our microanalysis quantitatively predicts the pseudopolymorphic transformation of our tested drug in small amounts and suggests that this particular method is a simple and convenient one that may be efficiently applied to polymorphic and pseudopolymorphic studies of a hygroscopic drug candidate, at even earlier development stages than the conventional method using glass bottles.