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Article / 2003

Vitro characterization of jet-milled and in-situ-micronized fluticasone-17-propionate

  • Hartwig Steckel
  • Peter Villax
  • Bernd Muller
International Journal of Pharmaceutics (2003), 258(1-2), 65-75

Particle properties are decisive for therapeutic efficiency of inhaled pulmonary drug. Jet-milling as the common way for micronization of inhaled powder drugs shows several disadvantages such as a non-homogeneous particle size distribution and unnatural, thermodynamically-activated particle surfaces causing a high agglomeration behavior. For pulmonary use a dry powder inhaler (DPI) beside a small particle size, a good de-agglomeration activity is required. this study, fluticasone-17-propionate (FP) is in-situ prepd. a respirable particle size by a controlled crystn. technique. First, the drug is dissolved acetone and pptd. by a solvent change method the presence of a cellulose ether (HPMC) as stabilizing hydrocolloid. By rapidly pouring the drug soln. into the polymer-rich water phase, the previously molecularly dispersed drug is assocd. to small particles and stabilized against crystal growth simultaneously by the presence of the hydrophilic polymer. This dispersion was then spray-dried. The meparticle size of the drug was around 2 mm and consequently the respirable range. The physico-chem. properties of the in-situ-micronized drug were compared to those of unmilled and a jet-milled quality. Differences the X-ray patterns and amorphous parts could be detected for the jet-milled but not for the in-situ-micronized drug. addn., the aerodynamic behavior of the engineered and the jet-milled FP was analyzed using the FlowCaps inhaler as delivery device and compared to the com. product Flutide Diskus.. The fine particle fraction (FPF) (<5 mm) was increased four-fold from approx. 9% for the jet-milled drug to approx. 40% for the in-situ-micronized drug when the pure drug powder was dispersed with the FlowCaps device.