Production and stabilization of olanzapine nanoparticles by rapid expansion of supercritical solutions (RESS)

• A drug poorly soluble in water was nanosized (150–350 nm).
• Successful production of olanzapine nanosuspensions was achieved by RESSAS.
• The rate of OLZ dissolution was increased significantly when processed by RESSAS.
• Steric hindrance or electrostatic stabilization promoted the stability of the suspension.

The purpose of the work was the production, stabilization and characterization of olanzapine (OLZ) nanoparticles by the RESS and RESSAS processes. A pilot scale unit for supercritical fluid processing was used for the production of RESS OLZ nanoparticles and RESSAS nanosuspensions. Supercritical OLZ-solution (scCO2, 20 MPa/50 °C) was expanded into air (RESS) or into an aqueous solution (HPMC, PEG, PEG + SLS, or polysorbate 80, RESSAS). Nanosuspensions were characterized for particle size, PSD and zetapotential. The freeze-dried nanoparticles were further evaluated for FTIR and OLZ dissolution rate. RESS OLZ could be produced with a mean particle size of 191.4 ± 9.6 nm, i.e., a 200-fold size reduction compared to the original anhydrous material. The material was partially amorphous, as confirmed by DSC and FTIR. The particle size of RESSAS OLZ nanosuspensions was in the same range. The highest stability (size and solid-phase) of nanosuspensions before and after freeze-drying was achieved when PEG + SLS were considered. In conclusion, the preparation of OLZ nanoparticles with improved dissolution rate and known solid-state forms was achieved by RESS and RESSAS processes.

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