Production of theophylline nanoparticles using rapid expansion of supercritical solutions with a solid cosolvent (RESS-SC) technique

• The production of theophylline nanoparticles by RESS-SC was examined.
• The availability of l-menthol or vanillin as a solid cosolvent was examined.
• l-Menthol was unsuitable for a solid cosolvent in the present conditions.
• Theophylline nanoparticles were obtained by use of vanillin as a solid cosolvent.
• Particle collection conditions have negligible effects on the particle sizes.

We report on the production of theophylline nanoparticles by rapid expansion of supercritical solutions with a solid cosolvent (RESS-SC) using CO2 with l-menthol or vanillin. The effects of particle collection conditions such as collection temperatures and spray distances on the theophylline nanoparticles produced were investigated in order to elucidate crystal growth mechanism of the present RESS-SC process. A liquid phase appeared at a pre-expansion section in the case of using l-menthol, and this suggests that it is unsuitable for a solid cosolvent in the present conditions. In the case of using vanillin, nano-sized particles of around 85 nm, which are about one-third as large as those produced by the conventional RESS technique, were obtained. Particle collection conditions have negligible effects on the particle sizes. This result suggests that crystal growth of theophylline particles crystallized in a collection vessel are blocked by crystallized vanillin particles those surrounds theophylline particles.

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