Quantitative analysis of pseudopolymorphic transformation of imidafenacin by application of a novel combination of near-infrared spectroscopy and a humidity-controlled 96-well plate

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. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.