Solid-state and particle size control of pharmaceutical cocrystals using atomization-based techniques

Int J Pharm. 2022 Jun 10:621:121798. doi: 10.1016/j.ijpharm.2022.121798. Epub 2022 May 4.

Abstract

Poor bioavailability and aqueous solubility represent a major constraint during the development of new API molecules and can influence the impact of new medicines or halt their approval to the market. Cocrystals offer a novel and competitive advantage over other conventional methods with respect towards the substantial improvement in solubility profiles relative to the single-API crystals. Furthermore, the production of such cocrystals through atomization-based methods allow for greater control, with respect to particle size reduction, to further increase the solubility of the API. Such atomization-based methods include supercritical fluid methods, conventional spray drying and electrohydrodynamic atomization/electrospraying. The influence of process parameters such as solution flow rates, pressure and solution concentration, in controlling the solid-state and final particle size are discussed in this review with respect to atomization-based methods. For the last decade, literature has been attempting to catch-up with new regulatory rulings regarding the classification of cocrystals, due in part to data sparsity. In recent years, there has been an increase in cocrystal publications, specifically employing atomization-based methods. This review considers the benefits to employing atomization-based methods for the generation of pharmaceutical cocrystals, examines the most recent regulatory changes regarding cocrystals and provides an outlook towards the future of this field.

Keywords: Antisolvent; Multicomponent systems; Nanoparticles; Precipitation; Regulatory; Spray drying; Supercritical fluids.

Publication types

  • Review

MeSH terms

  • Biological Availability
  • Crystallization / methods
  • Particle Size*
  • Pharmaceutical Preparations
  • Solubility

Substances

  • Pharmaceutical Preparations