Development and Validation of Particle Size Measurement for Mesalamine Nanocrystals Using Dynamic Light Scattering and Microscopic Techniques

The particle size measurement of drug nanocrystals is quite challenging due to solubility, aggregation, Ostwald ripening, non-spherical structure, sedimentation, and polydispersity nature of the particles. Dynamic light scattering (DLS) is frequently used for particle size determination of submicron-sized particles in both research and commercial manufacturing. Despite several advantages, particle size measurement and method development for drug nanocrystals using the DLS technique are limited due to repeatability and reproducibility issues. The present investigation aimed to develop the particle size method for mesalamine (MES) nanocrystals (NCs) using DLS. The method parameters such as solvent, sonication, concentration, temperature, and benchtop stability were screened, and the optimal method parameters were set to get repeatability and reproducibility. Three batches of MES NCs were used for method development, in which one center point batch and two random validation batches were taken. The determined particle size was 453.1 ± 27.1 nm with a polydispersity index (PDI) of 0.32 ± 0.05 for repeatability of the same center point batch. The mean particle size of three different center point batches was 465.4 ± 32.8 nm with a PDI of 0.49 ± 0.08, which revealed the reproducibility of the method and could be applied as a quality control tool in routine commercial manufacturing. The orthogonal microscopic techniques such as field emission scanning electron microscopy (FE SEM) and atomic force microscopy (AFM) were used to validate the DLS method. The results obtained from microscopic methods confirm the validity of the DLS method.