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Pharm Res. 2014 May;31(5):1239-53. doi: 10.1007/s11095-013-1245-7. Epub 2013 Nov 16.

A rifapentine-containing inhaled triple antibiotic formulation for rapid treatment of tubercular infection.

Author information

1
Respiratory Technology Group Woolcock Institute of Medical Research & Discipline of Pharmacology Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia.

Abstract

PURPOSE:

The potential for rifapentine-containing oral therapeutic regimens to significantly shorten the current six-month anti-tubercular treatment regimen is confounded by high plasma protein binding of rifapentine. Inhaled aerosol delivery of rifapentine, a more potent anti-tubercular antibiotic drug, in combination with other first-line antibiotics may overcome this limitation to deliver a high drug dose at the pulmonary site of infection.

METHODS:

A formulation consisting of rifapentine, moxifloxacin and pyrazinamide, with and without leucine, was prepared by spray-drying. This formulation was assessed for its physico-chemical properties, in vitro aerosol performance and antimicrobial activity.

RESULTS:

The antibiotic powders, with and without leucine, had similar median aerodynamic diameters of 2.58 ± 0.08 μm and 2.51 ± 0.06 μm, with a relatively high fine particle fraction of 55.5 ± 1.9% and 63.6 ± 2.0%, respectively. Although the powders were mostly amorphous, some crystalline peaks associated with the δ polymorph for the spray-dried crystalline pyrazinamide were identified.

CONCLUSIONS:

Stabilisation of the powder with 10% w/w leucine and protection from moisture ingress was found to be necessary to prevent overt crystallisation of pyrazinamide after long-term storage. In vitro biological assays indicated antimicrobial activity was retained after spray-drying. Murine pharmacokinetic studies are currently underway.

PMID:
24242939
DOI:
10.1007/s11095-013-1245-7
[Indexed for MEDLINE]

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