Solubility of probenecid in supercritical carbon dioxide and composite particles prepared using supercritical antisolvent process

Abstract

The solubilities of probenecid in supercritical carbon dioxide (CO2) were measured in terms of mole fraction ranging from 0.13 × 10−5 to 1.45 × 10−5 at temperatures from 313.2 K to 353.2 K and pressures from 15 MPa to 31 MPa. The solubility data were correlated with the dimensionally consistent Chrastil equation, Garlapati and Madras equation, Mendez-Santiago and Teja equation, Kumar and Johnston equation, and the Peng-Robinson equation of state to deviations of 12.3 %, 6.7 %, 9.7 %, 8.1 %, and 16.2 %, respectively. Due to the low solubility nature, supercritical antisolvent (SAS) process was used for designing composite particles of probenecid and poly(lactide-co-glycolide) (PLGA). The effects of operating parameters on particle morphology, recovery and drug loading were studied. Through SAS, PLGA coated probenecid particles were successfully obtained. The recovery could be higher than 80 %, and the probenecid concentration could be up to 75 mg/mL. Moreover, results of dissolution studies reveal the PLGA coated composite particles can accelerate the dissolution rate by about 10 and 2.4 times, comparing with the unprocessed probenecid and SAS-processed probenecid without PLGA.