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Preparation and characterisation of hydrocortisone particles using a supercritical fluids extraction process
Uppsala University, Department of Pharmacy, BMC.
Uppsala University, Department of Pharmacy, BMC.
2002 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 231, no 2, p. 155-66Article in journal (Refereed) Published
Abstract [en]

Crystallisation and subsequent milling of pharmaceutical powders by traditional methods often cause variations in physicochemical properties thereby influencing bioavailability of the formulation. Crystallisation of drug substances using supercritical fluids (SFs) offers some advantages over existing traditional methods in controlling particle characteristics. The novel particle formation method, solution enhanced dispersion by supercritical (SEDS) fluids was used for the preparation of hydrocortisone (HC) particles. The influence of processing conditions on the solid-state properties of the particles was studied. HC, an anti-inflammatory corticosteroid, particles were prepared from acetone and methanol solutions using the SEDS process. The solutions were dispersed with supercritical CO(2), acting as an anti-solvent, through a specially designed co-axial nozzle into a pressured vessel maintained at a specific constant temperature and pressure. The temperatures and pressures studied were 40-90 degrees C and 90-180 bar, respectively. The relative flow rates of drug solution to CO(2) were varied between 0.002 and 0.03. Solid-state characterisation of particles included differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), solubility studies and scanning electron microscopy (SEM) examination. The aerodynamic properties of SEDS prepared particles were determined by a multistage liquid impinger (MLI). Particles produced from acetone solutions were crystalline needles, melting at 221+/-2 degrees C. Their morphology was independent of processing conditions. With methanol solutions, particles were flakes or needles depending on the processing temperature and pressure. This material melted at 216+/-1 degrees C, indicating a different crystal structure from the original material, in agreement with observed differences in the position and intensity of the XRPD peaks. The simulated lung deposition, using the MLI, for HC powder was improved after SEDS processing. It was possible to produce and control the crystallinity, morphology, and aerodynamic properties of HC particles with the SEDS technique. This method may be useful for the processing of inhalation powders.

Place, publisher, year, edition, pages
2002. Vol. 231, no 2, p. 155-66
Identifiers
URN: urn:nbn:se:ltu:diva-11211DOI: 10.1016/S0378-5173(01)00870-5Local ID: a20974c0-e809-11db-b9a9-000ea68e967bOAI: oai:DiVA.org:ltu-11211DiVA, id: diva2:984160
Note

Upprättat; 2002; 20070411 (andbra)

Available from: 2016-09-29 Created: 2016-09-29 Last updated: 2017-11-24Bibliographically approved

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Velaga, Sitaram

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