Nano- and macro-geometrical structural change of caffeine and theophylline anhydrate tablets during hydration process by using X-ray computed tomography

The effects of nano- and macro-geometrical factors on the hydration kinetics of caffeine (CA) and theophylline anhydrate (TA) tablets at high humidity were investigated using X-ray high-resolution computed tomography (CT). Hydration profiles of CA and TA tablets obtained at 25 and 50 MPa, 96% relative humidity, and 20 °C were measured by weight and X-ray CT. The total tablet volume (G-V) and average tablet density (G-D) calculated based on the volume and weight of tablets, and tablet volume (CT-V) and tablet density (CT-D) were evaluated by X-ray CT. The hydration kinetics of CA and TA tablets followed two-dimensional growth of nuclei (Avrami-Erofee) and three-dimensional phase boundary equations, respectively. The increase in the G-V of TA tablets was initially more than, but later less than, that of CA tablets. The G-D of CA tablets varied extensively and was constant initially, whereas that of TA tablets decreased significantly in the initial stage. The CT-V of CA tablets gradually increased initially, but that of TA tablets increased significantly early on. The inter-granular volume (IG-V) of both tablets decreased initially with large fluctuations, but then increased. The CT-D of CA tablets decreased significantly, but that of TA tablets did not decrease. The hydration kinetics of CA and TA tablets was affected by changes in the geometrical structure of the tablets. X-ray CT is a powerful tool for evaluating dynamic changes inside tablets.