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

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.

• Authors: John Gar Yan Chan, Anneliese S Tyne, Angel Pang, Hak-Kim Chan, Paul M Young, Warwick J Britton, Colin C Duke, Daniela Traini
• Journal: Pharmaceutical research (Pharm Res) Vol. 31 Issue 5 Pg. 1239-53 (May 2014) ISSN: 1573-904X [Electronic] United States
• PMID: 24242939 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aerosols
• Antibiotics, Antitubercular
• Powders
• Rifampin
• rifapentine

Topics

• Administration, Inhalation
• Aerosols
• Animals
• Antibiotics, Antitubercular (administration & dosage, therapeutic use)
• Humans
• Mice
• Microbial Sensitivity Tests
• Microscopy, Electron, Scanning
• Particle Size
• Powder Diffraction
• Powders
• Rifampin (administration & dosage, analogs & derivatives, therapeutic use)
• Tuberculosis (drug therapy)