Stability and aerodynamic behaviour of glucocorticoid particles prepared by a supercritical fluids process
2004 (English)In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 21, no 4, 501-509 p.Article in journal (Refereed) Published
Particle processing techniques using supercritical fluids (SF) are potential alternative technologies to design particles for inhalation. Powders of budesonide and flunisolide were prepared using solution enhanced dispersion by supercritical fluids (SEDS) process. The aim was to determine thermodynamic stability of different polymorphs of flunisolide including new forms from SEDS technology and to characterise micronised and SEDS produced powders of budesonide and flunisolide for their suitability as inhalation powders. Acetone and methanol solutions of budesonide and flunisolide, with a concentration of 2.5 mg/ml, were used for the particle preparation. The pressure was 100 bar and temperatures were 60 °C or 80 °C. The flow rates of CO2 and drug solution were 9 ml/min and 0.3 ml/min, respectively. Chemical purity of different polymorphs of flunisolide was estimated using high performance liquid chromatography (HPLC) and thermal behaviour was determined using differential scanning calorimetry (DSC). Particle morphology and surface examination were performed using scanning electron microscopy (SEM) and atomic force microscopy (AFM), respectively. The particle size distribution and density of the powders were determined with the help of Coulter Counter and helium pycnometer respectively. The in vitro deposition of the powders was studied using multistage liquid impinger (MLI). From the stability study, it was found that the two forms of flunisolide, polymorphs II and hemihydrate, were the most stable. Flunisolide form III was transformed to hemihydrate during the stability study. The chemical purity of the material was increased after SEDS processing. SEDS produced powders of budesonide and flunisolide form III from acetone showed narrow volumetric particle size distributions with 90% of the particles below 4 μm and geometric mean size around 3 μm. However, in the MLI study, budesonide powder obtained from SEDS with acetone showed favorable deposition in the lower stages with a mass median aerodynamic diameter (MMAD) of around 3 μm whilst the flunisolide form III was preferentially deposited in the higher stages of the MLI with MMAD of over 5 μm, due to aggregation of the particles. Particles of budesonide and flunisolide, in the size range, suitable for inhalation, were reproducibly produced using SEDS.
Place, publisher, year, edition, pages
2004. Vol. 21, no 4, 501-509 p.
Chromatography; Supercritical Fluid/*methods, Drug Stability, Glucocorticoids/*chemical synthesis, Particle Size, Powders
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-91390DOI: 10.1016/j.ejps.2003.11.006PubMedID: 14998581OAI: oai:DiVA.org:uu-91390DiVA: diva2:164104