Structured emulsions in switchable soft-matter for formulating stable pharmaceutical microcrystal suspensions

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Long-acting drug delivery relies on crystalline suspensions with precise particle sizes for efficacy and stability.
• Current methods struggle to produce sub-10μm crystals with narrow, persistent size distributions.

Purpose of the Study:

• To develop a scalable bottom-up crystallization strategy for engineering stable, monodisperse microcrystal suspensions.
• To address the limitations of existing methods in controlling crystal size and stability for drug delivery.

Main Methods:

• Utilized pH-switchable structured emulsions as transient microreactors for anti-solvent crystallization.
• Employed a yield-stress soft-matter matrix to confine emulsion droplets and template active pharmaceutical ingredient (API) microcrystals.
• Investigated naproxen as a model API to form uniform microcrystals (approximately 7μm).

Main Results:

• Achieved highly uniform naproxen microcrystals (∼7μm) using the structured emulsion templating method.
• Demonstrated significantly reduced Ostwald ripening under accelerated stability conditions compared to conventional wet-bead milling.
• Preserved crystal form and maintained injectability-relevant particle size.

Conclusions:

• Structured emulsions provide a generalizable platform for engineering stable, monodisperse crystalline suspensions.
• The method is scalable via membrane emulsification and adaptable for various solid dosage forms.
• This approach enhances the reliability and long-term stability of long-acting drug delivery systems.