(402c) Study of Nimesulide Recrystallization Kinetics By Particle Sizing, Microscopy, and Raman

The stability of a common preclinical dosage form comprised of amorphous spray dried (ASD) material was studied using a new analytical probe developed by Blaze Metrics, that combines particle size, microscopy, and Particle Focused Raman spectroscopy. An amorphous dispersion of Nimesulide, a class of nonsteroidal anti-inflammatory drugs, was prepared by spray drying with HPMCAS-HG polymer. At a 10ml working scale, the stability of the ASD in differing concentrations of methyl cellulose was followed after exposure to serial dilutions in simulated gastric and intestinal fluids. Recrystallization kinetics were captured in the dual oral compartment model by simultaneously monitoring microscopy, particle size, and Particle Focused Raman using the single 3 in 1 probe. Samples were also taken, quenched, and analyzed by x-ray diffraction throughout the process as an independent monitor of crystallinity. It was found that increasing concentrations of methyl cellulose slowed the rate of recrystallization. While the microscopy, particle size, Raman and XRD results were all in agreement, Blaze in-process microscopy was able to detect recrystallization before the other techniques. Interestingly, the Particle Focused Raman spectroscopy revealed a short lived intermediate during the recrystallization process indicating a perhaps previously undiscovered form of Nimesulide. The insights from this data confirm the suitability and usefulness of this analytical probe technology for preformulations work. Additional (potential) applications in formulations will also be presented.