Abstract
The study evaluates the ability of extrudates to deliver coumarin particles micronized by the rapid expansion of supercritical solutions (RESS). The RESS parameters were drug load (2–50 g), pressure (15–42 MPa) and temperature (40–60°C) in the extraction and pressure in the expansion (0.1–5 MPa) chambers in batch or continuous and CO2 flow rate in the continuous mode of operation. Particles were characterized for size (laser diffractometry, optical and electronic microscopies—19–61 μm), surface area (BET—0.282–0.423 m2/g), density (pycnometry—1.273–1.358 g/cm3) and yield (2–70%). Extrudates were characterized for the force of extrusion (4 kN), release of coumarin (100%/24 h) and mechanical properties (bending strength and stiffness increased, whereas elasticity decreased in storage) and X-ray diffractometry (micronized particles and extrudates have shown identical patterns) and calorimetry (DSC, enthalpies increased on storage). In the discontinuous mode of operation, increased loads in the extraction or increased pressure in the expansion chambers led to larger particles, whereas increased temperature and pressure in the extraction chamber led to smaller particles. In the continuous mode of operation, a decrease on the expansion pressure, load and CO2 flow rate led to increased yields. An increase on the flow rate led to a decrease on the particles’ diameter, but an increase on coumarin load in the extraction chamber led to an increase in diameter. The study has identified the key parameters in RESS continuous and discontinuous modes of operation affecting the properties of the micronized coumarin particles and has proved the ability of extrudates with a laminar shape on delivering micronized particles.
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