Elimination of residual solvent from PLGA microspheres containing risperidone using supercritical carbon dioxide

This investigation aimed to eliminate the residual organic solvent dichloromethane (DCM) from microspheres containing risperidone using supercritical carbon dioxide (scCO2). A conventional emulsion-solvent evaporation procedure was used to prepare the microspheres, and scCO2 eliminated the residual DCM. To obtain the maximum elimination yield %, central composite design (CCD) with the parameters of static time, dynamic time, pressure, and temperature was applied. After scCO2 treatment, the residual DCM was analyzed using headspace GC-FID. Finally, the characterization, encapsulation efficiency, drug loading, and in-vitro release of the microspheres were also investigated. For maximum elimination % of residual DCM using scCO2 (99.43%), the static time, dynamic time, pressure, and temperature were 21.31 min, 119.17 min, 226.44 bar, and 44.77 °C, respectively. DCM contents of the risperidone-PLGA microspheres before and after scCO2 treatment were 4612 ± 198 μg/mL and <21.93 μg/mL, respectively. The mean particle sizes, pore diameter, and porosity after scCO2 treatment were higher than the pre-treatment values. ScCO2 technology could increase both porosity and DCM removal, which enhances the uniform distribution of the drug in the matrix. The microspheres before scCO2 treatment contains larger amounts of solvents, which could enhance polymeric chain mobility and thus drug release. Consequently, it leads to the sustained release of the drug from the microsphere matrix.