Evaluation of water induced phase transition of Fexofenadine Hydrochloride during wet granulation process using NIR and DSC techniques

Abstract The quality control of drug products during manufacturing processes is important, particularly the presence of different polymorphic forms in active pharmaceutical ingredients (API) during production, which could affect the performance of the formulated products. In this study, Fexofenadine Hydrochloride (FXD) Form I (anhydrous) was used as the starting material for pharmaceutical formulation, while FXD exhibited a polymorphic conversion to hydrate Form II in presence of water. It is necessary to monitor phase transition from Form I to Form II during wet granulation. The aim of this paper was to quantify the polymorphic forms of FXD during wet granulation process by NIR and DSC technique. Calibration models were developed and validated in binary mixtures of FXD polymorphs forms and multicomponent mixtures of FXD formulation. The NIR and DSC can be successfully employed to evaluate and quantify Form I during wet granulation. The Form I % determined was similar by NIR and DSC. The relationship between phase transition of FXD and water content was determined. In addition, the effect of various excipients on the phase transition of FXD was also evaluated by NIR. The understanding of the phase transition in wet granulation process of pure FXD, formulation and FXD-excipient mixtures provided directions for optimization of FXD manufacturing processes.