Physicochemical Evaluation of Carbamazepine Microparticles Produced by the Rapid Expansion of Supercritical Solutions and by Spray-Drying

Abstract

Purpose. To compare the physical and physicochemical characteristics of carbamazepine microparticles prepared using two different methods: (1) the rapid expansion of supercritical solutions (RESS) and (2) the spray-drying process. Methods. For both processes, microparticles were produced over a range of different temperatures (35 to 100°C). For the RESS method, carbon dioxide was the solvent used over a pressure range of 2500 to 3500 psi. As for the spray-drying method, different organic solvents were used at atmospheric pressure. Comparison was based on morphology, crystalline structure, mean particle size, and size distribution of processed particles. The influence of process parameters on microparticles' characteristics was also investigated. Particles were analyzed using scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), thermogravimetric analyzer (TGA), and differential scanning calorimetry (DSC). Results. The carbamazepine particles used as unprocessed starting material had a mean diameter of approximately 85 μm with a size distribution range between 15 and 336 μm. Microparticles produced by either the RESS or spray-drying method had a mean diameter smaller than 2 μm and a narrower size distribution range between 0.25 and 2.5 μm. SEM photomicrographs, X-ray diffractograms, and DSC spectra revealed that modification of crystal morphology was dependent on the operating conditions. Conclusions. Significant reduction in mean particle size and size distribution range of carbamazepine particles was observed by RESS and spray-drying methods. The results also demonstrate that the crystalline nature of carbamazepine particles depends on the method of production and on the operating parameters of pressure and temperature.

Keywords:

• Supercritical
• Spray-drying
• Carbon dioxide
• Polymorphism
• Carbamazepine
• Micronization