Recrystallization of two anti-cancer active pharmaceutical ingredients (APIs), erlotinib hydrochloride (erlotinib HCl) and fulvestrant, using supercritical antisolvent (SAS) process was investigated in this study. The most commonly used supercritical carbon dioxide was employed as the antisolvent. Effect of three process parameters including the operating temperature, pressure and solution flow rate have been studied. Analyses of the recrystallized erlotinib HCl and fulvestrant were examined by SEM, XRD and DSC. Erlotinib HCl was recrystallized from its mean particle size of 20 mu m to 2 mu m with different crystal habits. Different polymorphs of erlotinib HCl were obtained and confirmed from the XRD and DSC results. The prior art polymorph form A of erlotinib HCl showed enhanced dissolution rate by 3.6 times to its original polymorph form B. Significant particle size reduction was also obtained for fulvestrant. The mean particle size was reduced from its original value of 22 mu m to 2 mu m with much narrower particle size distribution. The cross-interaction effect between the operating temperature and pressure observed in the SAS treatment of fulvestrant was verified by the method of calculated mixture critical point (MCP). The micronized fulvestrant particles showed consistent polymorph as the original AP1, but with different crystal habits. It is confirmed that the SAS method is applicable for controlling the crystal properties of two APIs, erlotinib HCl and fulvestrant, which require rigorous control of physical characteristics. (C) 2010 Elsevier B.V. All rights reserved.