Steroid/mucokinetic hybrid nanoporous microparticles for pulmonary drug delivery
File Type:
PDFItem Type:
Journal ArticleDate:
2013Access:
OpenAccessCitation:
Tewes F, Paluch KJ, Tajber L, Gulati K, Kalantri D, Ehrhardt C, Healy AM, Steroid/mucokinetic hybrid nanoporous microparticles for pulmonary drug delivery, European Journal of Pharmaceutics and Biopharmaceutics, 85, 3, 2013, 604 - 613Download Item:
1-s2.0-S0939641113001094-main.pdf (Pre-print (author's copy) - Non-Peer Reviewed) 3.820Mb
Abstract:
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 ?m 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
Sponsor
Grant Number
Science Foundation Ireland (SFI)
Author's Homepage:
http://people.tcd.ie/ehrhardchttp://people.tcd.ie/healyam
http://people.tcd.ie/ltajber
Description:
PUBLISHEDType of material:
Journal ArticleSeries/Report no:
European Journal of Pharmaceutics and Biopharmaceutics85
3
Availability:
Full text availableSubject (TCD):
Immunology, Inflammation & Infection , Nanoscience & MaterialsDOI:
10.1016/j.ejpb.2013.03.020Licences: