Effect of solvent type on the nanoparticle formation of atorvastatin calcium by the supercritical antisolvent process

Min Soo Kim, Ha Seung Song, Hee Jun Park, Sung Joo Hwang

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


The aims of this study were to identify how the solvent selection affects particle formation and to examine the effect of the initial drug solution concentration on mean particle size and particle size distribution in the supercritical antisolvent (SAS) process. Amorphous atorvastatin calcium was precipitated from seven different solvents using the SAS process. Particles with mean particle size ranging between 62.6 and 1493.7 nm were obtained by varying organic solvent type and solution concentration. By changing the solvent, we observed large variations in particle size and particle size distribution, accompanied by different particle morphologies. Particles obtained from acetone and tetrahydrofuran (THF) were compact and spherical fine particles, whereas those from N-methylpyrrolidone (NMP) and dimethylsulfoxide (DMSO) were agglomerated, with rough surfaces and relatively larger particle sizes. Interestingly, the mean particle size of atorvastatin calcium increased with an increase in the boiling point of the organic solvent used. Thus, for atorvastatin particle formation via the SAS process, particle size was determined mainly by evaporation of the organic solvent into the antisolvent phase. In addition, the mean particle size was increased with increasing drug solution concentration. In this study, from the aspects of particle size and solvent toxicity, acetone was the better organic solvent for controlling nanoparticle formation of atorvastatin calcium.

Original languageEnglish
Pages (from-to)543-547
Number of pages5
JournalChemical and Pharmaceutical Bulletin
Issue number4
Publication statusPublished - 2012 Apr

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • Drug Discovery


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