Impact of pharmaceutical tablet properties on optical porosimetry performance.

Abstract

The porosity of a pharmaceutical tablet influences liquid transport, disintegration and dissolution, rendering its monitoring and control crucial for quality by design. Optical porosimetry, a non-destructive process analytical technology (PAT), combines gas in scattering media absorption spectroscopy (GASMAS), photon time-of-flight spectroscopy (PToFS), tablet thickness measurement and tablet solid refractive index. This article presents a short tutorial on optical porosimetry theory and a performance study of optical porosimetry on pharmaceutical tablets via design of experiments. The investigated tablets share the same formulation, solid refractive index and diameter but differ in porosity (∼0.05 and 0.25) and thickness (1, 3 and 5mm). Critical user-controllable factors impacting the measurement accuracy and precision of the investigated tablets were identified. These are the manufactured tablet thickness, porosity, the user-estimated solid refractive index, and the number of optical porosimetry measurements in decreasing order of significance. A comparison between tablet porosity measured by optical porosimetry and by nominal measurements revealed that optical porosimetry tends to overestimate the porosity of the investigated tablets, particularly at low porosities, and has greater variability. While optical porosimetry poses advantages as a non-destructive and rapid PAT for real-time release testing, users need to be aware of the appropriate range of tablet thickness, porosity and the solid refractive index estimate.