title: Controlled Expansion of Supercritical Solution: A Robust Method to Produce Pure Drug Nanoparticles With Narrow Size-Distribution.
abstract: We introduce a robust, stable, and reproducible method to produce nanoparticles based on expansion of supercritical solutions using carbon dioxide as a solvent. The method, controlled expansion of supercritical solution (CESS), uses controlled mass transfer, flow, pressure reduction, and particle collection in dry ice. CESS offers control over the crystallization process as the pressure in the system is reduced according to a specific profile. Particle formation takes place before the exit nozzle, and condensation is the main mechanism for postnucleation particle growth. A 2-step gradient pressure reduction is used to prevent Mach disk formation and particle growth by coagulation. Controlled particle growth keeps the production process stable. With CESS, we produced piroxicam nanoparticles, 60 mg/h, featuring narrow size distribution (176 ± 53 nm).
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5e, 00790 Helsinki, Finland; Division of Material Physics, Department of Physics, University of Helsinki, Gustaf Hällströmin katu 2a, 00560 Helsinki, Finland. Electronic address: jenni.pessi@helsinki.fi.
authors.forename: Jenni
authors.initials: J
authors.lastname: Pessi
authors.affiliation: Division of Material Physics, Department of Physics, University of Helsinki, Gustaf Hällströmin katu 2a, 00560 Helsinki, Finland.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Lassila
authors.affiliation: Division of Material Physics, Department of Physics, University of Helsinki, Gustaf Hällströmin katu 2a, 00560 Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Meriläinen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5e, 00790 Helsinki, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Räikkönen
authors.affiliation: Division of Material Physics, Department of Physics, University of Helsinki, Gustaf Hällströmin katu 2a, 00560 Helsinki, Finland.
authors.forename: Edward
authors.initials: E
authors.lastname: Hæggström
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5e, 00790 Helsinki, Finland.
authors.forename: Jouko
authors.initials: J
authors.lastname: Yliruusi
mesh_terms: D002245:Carbon Dioxide / Q000737:chemistry*; D003460:Crystallization; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods*; D004867:Equipment Design; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010894:Piroxicam / Q000737:chemistry; D011312:Pressure; D012996:Solutions; D013816:Thermodynamics
chemical_list: D004364:Pharmaceutical Preparations; D012996:Solutions; D010894:Piroxicam; D002245:Carbon Dioxide
keywords: crystal engineering; crystal growth; crystallization; drug delivery systems; nanoparticles; nanotechnology; nucleation; particle size; solid dispersion; supercritical fluids