Spray dried aerosol particles of salts for tuberculosis therapy

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dc.contributor.author Durham, P.G.
dc.contributor.author Zhang, Y.
dc.contributor.author German, N.
dc.contributor.author Mortensen, N.
dc.contributor.author Dhillon, J.
dc.contributor.author Mitchison, D.A.
dc.contributor.author Hickey, Anthony J.
dc.contributor.upauthor Fourie, P.B. (Petrus Bernardus)
dc.date.accessioned 2015-08-21T10:07:31Z
dc.date.available 2015-08-21T10:07:31Z
dc.date.issued 2015-08
dc.description.abstract Tuberculosis is the most serious infectious disease caused by a single organism, Mycobacterium tuberculosis (Mtb). The standard of care is a protracted and complex drug treatment regimen made more complicated and of longer duration by the incidence of multiple- and extensively drug resistant disease. Pulmonary delivery of aerosols as a supplement to the existing regimen offers the advantage of delivering high local drug doses to the initial site of infection and most prominent organ system involved in disease. Pyrazinamide is used in combination with other drugs to treat tuberculosis. It is postulated that the action of pyrazinoic acid (POA), the active moiety of pyrazinamide, may be enhanced by local pH adjustment, when presented as a salt form. POA was prepared as leucine (POA-leu) and ammonium salts (POA-NH4), spray dried and characterized in terms of physico-chemical properties (melting point, crystallinity, moisture content), aerodynamic performance (aerodynamic particle size distribution, emitted dose) and in vitro inhibitory effect on two mycobacteria (Mtb and Mycobacterium bovis) . Particles were prepared in sizes suitable for inhalation (3.3 and 5.4m mass median aerodynamic diameter and 61 and 40% of the aerodynamic particle size distribution less than 4.46m, as measured by inertial impaction, for POA-leu and POANH4, respectively) and with properties (stoichiometric 1:1 ratio of salt to drug, melting points at ~180C, with water content of <1%) that would support further development as an inhaled dosage form. In addition, POA salts demonstrated greater potency in inhibiting mycobacterial growth compared with POA alone which is promising for therapy. en_ZA
dc.description.embargo 2016-08-31 en_ZA
dc.description.librarian hb2015 en_ZA
dc.description.uri http://pubs.acs.org/journal/mpohbp en_ZA
dc.identifier.citation Durham, PG, Zhang, Y, German, N, Mortensen, N, Dhillon, J, Mitchison, DA, Fourie, PB & Hickey, AJ 2015, 'Spray dried aerosol particles of salts for tuberculosis therapy', Molecular Pharmaceutics, vol. 12, no. 8, pp. 2574-2581. en_ZA
dc.identifier.issn 1543-8384 (print)
dc.identifier.issn 1543-8392 (online)
dc.identifier.other 10.1021/acs.molpharmaceut.5b00118
dc.identifier.uri http://hdl.handle.net/2263/49428
dc.language.iso en en_ZA
dc.publisher American Chemical Society en_ZA
dc.rights This document is the Accepted Manuscript version of a Published Work that appeared in final form in Organometallics, © 2015 American Chemical Society after peer review and technical editing by the publisher. en_ZA
dc.subject Aerosol particles en_ZA
dc.subject Tuberculosis therapy en_ZA
dc.subject Pyrazinamide en_ZA
dc.subject Mycobacterium tuberculosis (MTB) en_ZA
dc.subject Pyrazinoic acid (POA) en_ZA
dc.title Spray dried aerosol particles of salts for tuberculosis therapy en_ZA
dc.type Postprint Article en_ZA


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