Recrystallization and Production of Spherical Submicron Particles of Sulfasalazine Using a Supercritical Antisolvent Process

Wei-Yi Wu,Chie-Shaan Su

doi:10.3390/cryst8070295

Abstract

In this study, the recrystallization and production of spherical submicron particles of sulfasalazine, an active pharmaceutical ingredient (API), were performed using the supercritical antisolvent (SAS) process, a nonconventional crystallization technique. Sulfasalazine was dissolved in tetrahydrofuran (THF), and supercritical carbon dioxide (CO2) served as the antisolvent. The effects of operating parameters on the SAS process, including the operating pressure, solution concentration, solution flowrate, CO2 flowrate, and spraying nozzle diameter, at two operating temperatures were examined. The solid-state characteristics of sulfasalazine before and after the SAS process, including particle size, crystal habit, and crystal form, were analyzed using a scanning electron microscope (SEM), powder X-ray diffractometer (PXRD), and differential scanning calorimeter (DSC). A higher operating temperature, intermediate operating pressure, higher CO2 flowrate, and lower solution flowrate are recommended to obtain spherical particles of sulfasalazine. The effects of the solution concentration and spraying nozzle diameter on the SAS process were negligible. Under optimal conditions, spherical sulfasalazine crystals with a mean size of 0.91 μm were generated, and this study demonstrated the feasibility for tuning the solid-state characteristics of API through the SAS process.

Highlights

In the pharmaceutical industry, the modification of the solid-state characteristics of active pharmaceutical ingredients (APIs) is crucial to overcome poor aqueous solubility and provide suitable powder characteristics in downstream processing [1]
Reducing the particle size, modifying the crystal habit, and designing the crystal form of APIs are common approaches to improve the bioavailability of APIs with poor water solubility and to enhance powder handling in the formulation design [2]
supercritical antisolvent (SAS), the THFtemperature was selected as an aappropriate solvent supercritical served as the antisolvent, and operating exerted significant effect on when the crystal habit

Summary

Introduction

The modification of the solid-state characteristics of active pharmaceutical ingredients (APIs) is crucial to overcome poor aqueous solubility and provide suitable powder characteristics in downstream processing [1]. Reducing the particle size, modifying the crystal habit, and designing the crystal form of APIs are common approaches to improve the bioavailability of APIs with poor water solubility and to enhance powder handling in the formulation design [2]. Modi et al investigated the effect of crystal habit on intrinsic dissolution behavior and demonstrated the effect of particle-level properties and the surface molecular environment on the intrinsic dissolution rate [4]. Chattoraj and Sun summarized different crystal and particle engineering strategies for improving powder flow and compression properties for continuous tablet manufacturing through direct compression [5]. Pudasaini et al investigated the effect of solvent selection on crystal habit to overcome problems in needle-like crystal production through a conventional crystallization process [6]

Methods

Results

Conclusion