Determination of water penetration and drug concentration profiles in HPMC-based matrix tablets by near infrared chemical imaging.

This work describes methodologies based on near infrared chemical imaging (NIR CI) and chemometric data analysis for studying hydration behaviors of prolonged release tablets, which contain a high solubility drug at high load and a hydrophilic polymer hydroxypropylmethylcellulose (HPMC). Hydration studies were performed by suspending the tablets in water at ambient temperature. The hydrated tablets were then dissected and scanned by NIR CI. Single wavelength images were obtained for accurately measuring radial dimension of the gel layer and size of the tablet core. By performing a principal component analysis (PCA), the phenomenon of polymer phase transition from the glassy state to rubbery state was detected and visualized. Partial least squares (PLS) models were created for quantitative analysis of the active pharmaceutical ingredient (API) and relative concentration of water in the hydrated tablets. The API concentration profiles are suitable for defining the swelling front in hydrated tablets. Because the NIR CI results are pixel-specific and each pixel has its unique coordinates, it is feasible to analyze and present the results according to spatial locations. The physical and chemical changes at the swelling/diffusion fronts can be demonstrated by overlaying the PCA and PLS results, which shed light on the release mechanism.