The use of in situ near infrared imaging and Raman mapping to study the disproportionation of a drug HCl salt during dissolution

NIR imaging and Raman mapping of the dissolution of model pharmaceutical formulations containing the HCl salt of a developmental compound, were carried out using a custom designed flow through cell. The results of this work have shown that NIR imaging and Raman mapping are capable of monitoring the distribution of the components in a formulation during dissolution while also revealing any form changes which may occur in real time. The NIR and Raman data revealed that the drug underwent conversion to the free base when water was used as the dissolution medium. However, in 0.1 M HCl this conversion was no longer seen as the medium was below the pH(max) (the pH of saturation of both unionised and ionised species and above which the free base can form) of the drug. The data from both approaches broadly agreed demonstrating the applicability of these methods to studying and enhancing our understanding of the complex physical and chemical processes which occur during dissolution in real time. (C) 2015 Elsevier B.V. All rights reserved.