Acoustic assessment of mean grain size in pharmaceutical compacts

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.