Chemical Imaging of Oral Solid Dosage Forms and Changes upon Dissolution Using Coherent Anti-Stokes Raman Scattering Microscopy

TLDR

Dissolution testing is essential for evaluating pharmaceutical dosage forms, yet solid‑state properties of components can unpredictably alter dissolution, underscoring the need to monitor and visualize these properties during testing. This study aimed to employ coherent anti‑Stokes Raman scattering microscopy to visualize the solid‑state behavior of lipid‑based oral dosage forms containing theophylline anhydrate during real‑time dissolution. CARS microscopy tracked drug release with ~1.5 µm spatial resolution and revealed the spatial transformation of theophylline anhydrate into its less soluble monohydrate during dissolution. The results showed that the formulation method affects theophylline’s physicochemical behavior, with monohydrate formation observed on tablets compressed from powdered mixtures but not on solid lipid extrudates.

Abstract

Dissolution testing is a crucial part of pharmaceutical dosage form investigations and is generally performed by analyzing the concentration of the released drug in a defined volume of flowing dissolution medium. As solid-state properties of the components affect dissolution behavior to a large and sometimes even unpredictable extent there is a strong need for monitoring and especially visualizing solid-state properties during dissolution testing. In this study coherent anti-Stokes Raman scattering (CARS) microscopy was used to visualize the solid-state properties of lipid-based oral dosage forms containing the model drug theophylline anhydrate during dissolution in real time. The drug release from the dosage form matrix was monitored with a spatial resolution of about 1.5 μm. In addition, as theophylline anhydrate tends to form the less soluble monohydrate during dissolution, CARS microscopy allowed the solid-state transformation of the drug to be spatially visualized. The results obtained by CARS microscopy revealed that the method used to combine lipid and active ingredient into a sustained release dosage form can influence the physicochemical behavior of the drug during dissolution. In this case, formation of theophylline monohydrate on the surface was visualized during dissolution with tablets compressed from powdered mixtures but not with solid lipid extrudates.