A novel inhalable form of rifapentine

John G. Y. Chan, Colin C. Duke, Hui Xin Ong, Joseph C. Y. Chan, Anneliese S. Tyne, Hak-Kim Chan, Warwick J. Britton, Paul M. Young, Daniela Traini

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Recent murine studies found that rifapentine, dosed daily, at least halved tuberculosis treatment times compared with standard rifampicin and isoniazid-containing regimens. However, in humans, an inhalable form of rifapentine may be necessary to considerably shorten treatment duration because of the physiological barriers associated with oral therapy. The current study compares two inhalable rifapentine dry powders—a novel pure crystalline form and an amorphous form—by a series of in vitro tests. The crystalline and amorphous powders had a mass median aerodynamic size of 1.68 ± 0.03 and 1.92 ± 0.01 μm, respectively, associated with a fine particle fraction of 83.2 ± 1.2% and 68.8 ± 2.1%, respectively. A quinone degradation product was identified in the amorphous powder stored for 1 month, whereas the crystalline form remained chemically stable after storage at both 0% and 60% relative humidity, 25°C, for at least 3 months. Solubilized rifapentine was well tolerated by pulmonary tissue and macrophage cells up to approximately 50 μM. The accumulation of rifapentine within alveolar macrophage cells was significantly higher than for rifampicin, indicating enhanced delivery to infected macrophages. The novel inhalable crystalline form of rifapentine is suitable for targeted treatment of tuberculosis infection and may radically shorten treatment duration.
Original languageEnglish
Pages (from-to)1411-1421
Number of pages11
JournalJournal of Pharmaceutical Sciences
Volume103
Issue number5
DOIs
Publication statusPublished - 2014
Externally publishedYes

Keywords

  • aerosols
  • pulmonary
  • crystallization
  • FTIR
  • HPLC
  • NMR
  • thermal analysis
  • X-ray powder diffractometry

Fingerprint

Dive into the research topics of 'A novel inhalable form of rifapentine'. Together they form a unique fingerprint.

Cite this