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Steroid/mucokinetic hybrid nanoporous microparticles for pulmonary drug delivery

Résumé : In a number of pulmonary diseases, patients may develop abnormally viscous mucus reducing drug efficacy. To increase budesonide diffusion within lung fluid, we developed nanoporous microparticles (NPMPs) composed of budesonide and a mucokinetic, ambroxol hydrochloride, to be inhaled as a dry powder. Budesonide/ambroxol-HCl particles were formulated by spray drying and characterised by various physicochemicals methods. Aerodynamic properties were evaluated using a cascade impactor. Drugs apparent permeability coefficients were calculated across mucus producing Calu-3 cell monolayers cultivated at an air–liquid interface. Microparticles made only from budesonide and ambroxol-HCl had smooth surfaces. In the presence of ammonium carbonate ((NH4)2CO3), NPMPs were formulated, with significantly (P < 0.05) superior aerodynamic properties (MMAD = 1.87 ± 0.22 μm and FPF = 84.0 ± 2.6%). The formation of nanopores and the increase in the specific surface area in the presence of (NH4)2CO3 were mainly attributed to the neutralisation of ambroxol-HCl to form ambroxol base. Thus, ambroxol base could behave in the same manner as budesonide and prompt nanoprecipitation when spray dried from an ethanol/water mix occurs. All formulations were amorphous, which should enhance dissolution rate and diffusion through lung fluid. These NPMPs were able to improve budesonide permeability across mucus producing Calu-3 cell monolayers (P < 0.05) suggesting that they should be able to enhance budesonide diffusion in the lungs through viscous mucus.
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Contributor : Frederic Tewes <>
Submitted on : Tuesday, January 13, 2015 - 3:58:41 PM
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Frederic Tewes, Krzysztof Paluch, Lidia Tajber, Karan Gulati, Devesh Kalantri, et al.. Steroid/mucokinetic hybrid nanoporous microparticles for pulmonary drug delivery. European Journal of Pharmaceutics and Biopharmaceutics, Elsevier, 2013, 85 (3), pp.604-613. ⟨10.1016/j.ejpb.2013.03.020⟩. ⟨inserm-01102852⟩

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