Fractal analysis of SEM images and mercury intrusion porosimetry data for the microstructural characterization of microcrystalline cellulose-based pellets

The microstructure of theophylline pellets prepared from microcrystalline cellulose, carbopol and dicalcium phosphate dihydrate, according to a mixture design, was characterized using textural analysis of gray-level scanning electron microscopy (SEM) images and thermodynamic analysis of the cumulative pore volume distribution obtained by mercury intrusion porosimetry. Surface roughness evaluated in terms of gray-level non-uniformity and fractal dimension of pellet surface depended on agglomeration phenomena during extrusion/spheronization. Pores at the surface, mainly 1–15 μm in diameter, determined both the mechanism and the rate of theophylline release, and a strong negative correlation between the fractal geometry and the b parameter of the Weibull function was found for pellets containing >60% carbopol. Theophylline mean dissolution time from these pellets was about two to four times greater. Textural analysis of SEM micrographs and fractal analysis of mercury intrusion data are complementary techniques that enable complete characterization of multiparticulate drug dosage forms.