Visualization of Component Distribution and Determination of Particle Size in Wet Granulation Tablets Based on Raman Imaging

Abstract

Raman imaging was used to detect the distribution of each component of wet granulation tablets and analyze their active pharmaceutical ingredient (API) particle size. The four excipients in the tablets — lactose, microcrystalline cellulose, crosslinked sodium carboxymethyl cellulose, and magnesium stearate — were significantly identified by their characteristic peaks, respectively. The average equivalent diameters of API particles in tablets 1, 2, and 3 were 4.49, 6.53, and 13.95 μm, respectively. Tablet 1 exhibited a favorable particle morphology, with minimal differences between particles and an average particle size. The greatest particle size disparities were observed in tablet 3. Furthermore, the cumulative distribution statistics ratio in the API particle system reached 90%, showing that the particle sizes of tablets 1, 2, and 3 were 5.41, 14.45, and 24.00 μm, respectively. This trend was consistent with the API powder results for raw materials measured using a particle size analyzer. The minimum detection limit of the particles was 1.68 μm. In addition, the introduction of the coefficient of variation was used to evaluate the tablets’ uniformity. Whereas tablet 3 exhibited the highest degree of variability and the poorest uniformity, tablet 2 exhibited the lowest degree of variation and the best uniformity. Raman imaging facilitated the visualization of the distribution of each component in the tablet and the API particle size analysis in a «one-stop» manner.