Particle size design of acetaminophen using supercritical carbon dioxide to improve drug delivery: Experimental and modeling

Abstract

In this communication, micronized acetaminophen particles are investigated using the rapid expansion of the supercritical solution (RESS) process. According to the obtained results, the largest acetaminophen particle size was ≤ 40 nm with spherical and quasi-spherical morphology in comparison with unprocessed particles with needle shape and mean particle size of 80.32 µm. The effect of extraction pressure and temperature, pre-expansion temperature, and spaying distance on the acetaminophen particle size and morphology were studied. The results indicated that increases in the extraction pressure and temperature led to decreases acetaminophen particle size but increasing pre-expansion temperature and spaying distance had opposite effects. To investigate particle formation through the RESS process with more details, velocity, pressure, density, and temperature behavior of the supercritical solution and acetaminophen solubility in supercritical CO2 was modeled. Ultimately, the population balance equation was solved based on the moment method and acetaminophen particle size distribution was predicted and the influence of coagulation phenomenon as a remarkable mechanism on particle size distribution was investigated.