Particle preparation of pharmaceutical compounds using supercritical antisolvent process: current status and future perspectives

Drug Deliv Transl Res. 2023 Apr;13(4):946-965. doi: 10.1007/s13346-022-01283-7. Epub 2022 Dec 27.

Abstract

The low aqueous solubility and subsequently slow dissolution rate, as well as the poor bioavailability of several active pharmaceutical ingredients (APIs), are major challenges in the pharmaceutical industry. In this review, the particle engineering approaches using supercritical carbon dioxide (SC CO2) as an antisolvent are critically reviewed. The different SC CO2-based antisolvent processes, such as the gas antisolvent process (GAS), supercritical antisolvent process (SAS), and a solution-enhanced dispersion system (SEDS), are described. The effect of process parameters such as temperature, pressure, solute concentration, nozzle diameter, SC CO2 flow rate, solvent type, and solution flow rate on the average particle size, particle size distribution, and particle morphology is discussed from the fundamental perspective of the SAS process. The applications of the SAS process in different formulation approaches such as solid dispersion, polymorphs, cocrystallization, inclusion complexation, and encapsulation to enhance the dissolution rate, solubility, and bioavailability are critically reviewed. This review highlights some areas where the SAS process has not been adequately explored yet. This review will be helpful to researchers working in this area or planning to explore SAS process to particle engineering approaches to tackle the challenge of low solubility and subsequently slow dissolution rate and poor bioavailability.

Keywords: Antisolvent; Carbon dioxide; Encapsulation; Solid dispersion; Solubility; Supercritical.

Publication types

  • Review

MeSH terms

  • Carbon Dioxide* / chemistry
  • Particle Size
  • Solubility
  • Solutions
  • Solvents / chemistry
  • Temperature
  • Water*

Substances

  • Carbon Dioxide
  • Solvents
  • Solutions
  • Water