کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2481655 | 1556274 | 2008 | 13 صفحه PDF | دانلود رایگان |
Challenges in reformulating pressurized metered-dose inhalers (pMDIs) with hydrofluoroalkane (HFA) propellants, and the potential of inhalation formulations for the delivery of drugs to and through the lungs have encouraged the development of novel suspension-based pMDI formulations. In this work we propose a new methodology for engineering polar drug particles with enhanced stability and aerosol characteristics in propellant HFAs. The approach consists in ‘trapping’ HFA-philic moieties at the surface of particles, which are formed using a modified emulsification–diffusion method. The trapped moieties act as stabilizing agents, thus preventing flocculation of the otherwise unstable colloidal drug particles. This approach has advantages compared to surfactant-stabilized colloids in that no free stabilizers remain in solution (reduced toxicity), and the challenges associated with the synthesis of well-balanced amphiphiles are circumvented. The methodology was tested by trapping polyethylene glycol (PEG) at the surface of particles of a model polar drug—salbutamol sulfate. Colloidal probe microscopy is used to quantitatively demonstrate the trapping of the HFA-phile at the surface, and the ability of PEG in screening particle–particle cohesive interactions. Both physical stability and the corresponding aerosol characteristics are significantly improved compared to those of a commercial formulation. The fine particle fraction of PEG-coated salbutamol sulfate was observed to be 42% higher than that of Ventolin HFA®. The formation of stable dispersions of terbutaline hemisulfate using the same approach, suggests this to be a generally applicable methodology to polar drugs.
Journal: European Journal of Pharmaceutical Sciences - Volume 33, Issue 2, 5 February 2008, Pages 146–158