Gas anti-solvent processing of a new sulfamethoxazole-L-malic acid cocrystal

Abstract The objective of this work was to enhance the dissolution rate of a poorly water-soluble antibiotic drug, sulfamethoxazole (SMX), by forming cocrystal with l -malic acid (MA) using gas anti-solvent (GAS) process. The effect of SMX to MA mass ratio (2:1, 1.5:1 and 1:1) on drug content and dissolution rate was investigated. The GAS cocrystallization was carried out at 45 °C using the drug concentration of 50% saturation in acetone. It was found that cocrystals produced from SMX to MA ratio of 2:1 had higher drug content than those produced from the ratios 1.5:1 and 1:1. In the dissolution studies, it was found that 90% of SMX in the cocrystals could be dissolved within 4.2 min, whereas the times required to dissolve 90% of the drug in the physical mixtures were 8.2 min (ratio 1:1) and 25 min (ratio 2:1), and up to 28 min for the micronized SMX.