Acoustic assessment of mean grain size in pharmaceutical compacts

Abstract

An ultrasonic non-destructive technique for the microstructure length-scale characterization of solid dosage pharmaceutical tablets is presented. The technique is based on the relationship between the attenuation of longitudinal ultrasonic elastic waves and the size of micro-structural features in the tablet material. In the reported experiments, the ultrasonic attenuation in microcrystalline cellulose (MCC)–lactose monohydrate (LMH) blended pharmaceutical compacts is measured by means of two pitch-catch experiments. The frequency dependent attenuation coefficient for the MCC–LMH compacts is then related to the mean grain diameter for each compact. For verification purposes, the mean grain diameter of the compacts was also established using micro-scale X-ray computerized tomography (MicroXCT). The mean grain diameters established by both routines agree well, and support the efficacy of the ultrasonic attenuation technique. The microstructure of a pharmaceutical compact (i.e., grain sizes and micro-feature size distribution) has been shown to have a profound effect on its mechanical properties, namely hardness, porosity, and mass density distribution, and in turn, can critically impact the dissolution profile and structural integrity of a compact. The ultrasonic technique presented provides a non-destructive and rapid method for determining the mean grain diameter size for powder compacts, thus providing a more timely and cost-effective method, compared to traditional techniques, of characterizing a compact's internal microstructure.