Recrystallization and Micronization of Camptothecin by the Supercritical Antisolvent Process: Influence of Solvents

Recrystallization and micronization of camptothecin (CPT), a potent anticancer agent, has been performed using the supercritical antisolvent (SAS) process in this study. The effect of different solvents on the morphology, mass median diameter (Dp(50)), particle size distribution (PSD) and the crystallinity of obtained CPT microparticles was investigated in detail. Five pure solvents, acetic acid, dimethylformamide, chloroform, N-methyl-2-pyrrolidone, dimethyl sulfoxide (DMSO), and a series of solvent mixture of ethanol/DMSO with different volume ratios (R), where R was defined as the ethanol volume to total solvent volume, were selected as solvents. The raw CPT and processed CPT particles were characterized using SEM, laser diffraction particle size analysis, FT-IR spectroscopy, LC-MS, powder XRD, and DSC. The processed CPT microparticles were flake-like and much thinner and more uniform than the lamelliform CPT raw material. The Dp(50) of the processed CPT ranged from 0.39 to 2.14 mu m, and the PSD of the processed CPT microparticles became much narrower. Solvents with a higher ratio of density and viscosity, lower surface tension, and lower solvation power will form smaller CPT microparticles with lower crystallinity, which helps to improve the solubility of CPT in biological liquids. Furthermore, the addition of ethanol into DMSO improves the properties of DMSO and decreases the CPT solubility, which is beneficial to the acquisition of smaller particles, and the particle size decreased significantly with the increase of R. The chemical structure and crystalline structure of CPT did not change after the SAS process. However, the crystallinity of the obtained CPT microparticles was less than that of raw CPT, and varied for different solvents.