Microparticle Production of Active Pharmaceutical Ingredient Using Supercritical Antisolvent Process: A Case Study of Allopurinol

Abstract

Allopurinol is a relatively water-insoluble drug and, consequently, its efficacy was frequently limited by the dissolution or solubility phenomena. The purpose of this study was to improve the solid-state properties and dissolution behavior of allopurinol via a supercritical antisolvent (SAS) process using CO2 as an antisolvent. The effects of operating parameters: temperature (35–55 °C), pressure (80–100 bar), solution concentration (8–15 mg/mL), CO2 flow rate (2–4 L/min), and solution flow rate (0.25–0.50 mL/min) were studied. Moreover, the physical properties of unprocessed and SAS-processed allopurinol were analyzed by SEM, FTIR, DSC, TGA, and PXRD. The dissolution rate of unprocessed and SAS-processed allopurinol was also investigated and compared. In this case study, allopurinol was effectively micronized from 15.3 μm to 1.35 μm at the optimal operating condition. The results verify that the solid-state properties and dissolution rate of allopurinol can be controlled and improved via the micronization process by using SAS technology.

Keywords

• microparticle production
• supercritical antisolvent
• carbon dioxide
• allopurinol