NIR Based Approach to Evaluate Anhydrate-hydrate Transformations

Abstract

The spectroscopic techniques (viz. Near Infrared Spectroscopy, Raman Spectroscopy etc.) are widely used as Process Analytical Technology (PAT) tools supporting the Quality by Design (QbD) Concept. Furthermore, advancements in multivariate data analysis approaches have enabled extraction of information from complex dataset. The present study focuses on evaluating the feasibility of NIR spectroscopy as a PAT tool to understand phase transformations of anhydrate and hydrate forms of naproxen sodium (NS) during pharmaceutical development. NS is known to exist in anhydrate, various hydrate and solvate forms1,2,3. In the present study, four solid forms of NS i.e. anhydrate, monohydrate, dihydrate and tetrahydrate forms were used. The monohydrate form was generated by recrystallization from 64 mol% methanol. The dihydrate and tetrahydrate forms were generated by exposing the anhydrate form at higher relative humidity conditions. The generated solid forms were confirmed by PXRD (Powder X-Ray Diffraction). The NIR spectra were evaluated using multivariate data analysis (Principle Component Analysis (PCA)). The identity and phase purity of the solid forms were confirmed by PXRD measurements. The NIR spectra were also distinct among the four solid forms. Scores plot of PCA depicted good separation among the four solid forms. The loadings plots (PC1 and PC2) indicated that the C-H and O-H spectral regions were most contributing to the separation observed in the scores plot. Thus, the present study indicates the feasibility of NIR spectroscopy to efficiently monitor phase transformation of NS. Future studies will focus on development of NIR based quantitative model that can be applied for online monitoring of hydrate formation and dehydration behaviour of the NS solid forms during processing and storage.