Micronization of sulfamethoxazole using the supercritical anti-solvent process

Abstract

Micronization of an antibiotic compound sulfamethoxazole was investigated in this study using the supercritical anti-solvent (SAS) precipitation method. The results from either the batch or continuous process were compared, and the latter one yielded smaller particles. Effects on particle size due to various process parameters in the continuous SAS process (the concentration and the flow rate of the solution of sulfamethoxazole, the operating pressure and temperature) had been studied through a fractional factorial design for sulfamethoxazole. The experimental results showed that there was a significant interaction between the parameters of the flow rate and the concentration of the sulfamethoxazole solution. Analyses of the micronized sulfamethoxazole particles were examined using SEM, XRD and DSC. Sulfamethoxazole was micronized from its original size of 41.7 to 5.1 μm. The micronized sulfamethoxazole exhibited a higher dissolution rate in a simulated intestinal fluid than that of the original compound. It was further demonstrated that the co-precipitation of sulfamethoxazole with a hydrophilic polymer hydroxypropyl cellulose (HPC) in the continuous SAS process provided more enhanced dissolution rate.