Sorbitol-coated indomethacin and naproxen particles produced by supercritical CO2-assisted spray drying

Abstract

Co-spraying active pharmaceutical ingredients (APIs) with excipients is a strategy to create excipient matrices containing API particles to address formulation challenges such as the reconstitution of powders into homogeneous suspensions. In this work, indomethacin and naproxen were co-sprayed with/without sorbitol using supercritical CO2-assisted spray drying (SASD), followed by particle collection in a filter paper, and resuspension in an aqueous excipient solution. SASD yielded particles in the range of 0.4–7.6 µm, naproxen crystalline Form 1 particles in an amorphous sorbitol matrix, and a partially crystalline indomethacin-sorbitol mixture. Most naproxen-sorbitol mixtures successfully constituted homogenous microparticle suspensions where sorbitol matrix dissolved upon contact with water releasing naproxen particles, while indomethacin-sorbitol mixtures were not reconstitutable and not studied further. The API-sorbitol interactions were studied in detail by thermal analysis and COSMO-RS modelling. Overall, the work presented herein provides a better understanding of co-spraying of APIs with excipients for the formulation of reconstitutable dried microparticles.