Development and Characterization of a Dry Powder Formulation for Anti-Tuberculosis Drug Spectinamide 1599

Ian E. Stewart, Pradeep B. Lukka, Jiuyu Liu, Bernd Meibohm, Mercedes Gonzalez-Juarrero, Miriam S. Braunstein, Richard E. Lee, Anthony J. Hickey

Research output: Contribution to journalArticle

Abstract

Purpose: Human tuberculosis (TB) is a global health problem that causes nearly 2 million deaths per year. Anti-TB therapy exists, but it needs to be administered as a cocktail of antibiotics for six months. This lengthy therapy results in low patient compliance and is the main reason attributable to the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis. Methods: One alternative approach is to combine anti-TB multidrug therapy with inhalational TB therapy. The aim of this work was to develop and characterize dry powder formulations of spectinamide 1599 and ensure in vitro and in vivo delivered dose reproducibility using custom dosators. Results: Amorphous dry powders of spectinamide 1599 were successfully spray dried with mass median aerodynamic diameter (MMAD) = 2.32 ± 0.05 μm. The addition of L-leucine resulted in minor changes to the MMAD (1.69 ± 0.35 μm) but significantly improved the inhalable portion of spectinamide 1599 while maintaining amorphous qualities. Additionally, we were able to demonstrate reproducibility of dry powder administration in vitro and in vivo in mice. Conclusions: The corresponding systemic drug exposure data indicates dose-dependent exposure in vivo in mice after dry powder intrapulmonary aerosol delivery in the dose range 15.4 - 32.8 mg/kg.

Original languageEnglish (US)
Article number136
JournalPharmaceutical Research
Volume36
Issue number9
DOIs
StatePublished - Sep 1 2019

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Powders
Tuberculosis
Pharmaceutical Preparations
Aerodynamics
Therapeutics
Patient Compliance
Medical problems
Aerosols
Mycobacterium tuberculosis
Leucine
Anti-Bacterial Agents
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Cite this

Stewart, I. E., Lukka, P. B., Liu, J., Meibohm, B., Gonzalez-Juarrero, M., Braunstein, M. S., ... Hickey, A. J. (2019). Development and Characterization of a Dry Powder Formulation for Anti-Tuberculosis Drug Spectinamide 1599. Pharmaceutical Research, 36(9), [136]. https://doi.org/10.1007/s11095-019-2666-8

Development and Characterization of a Dry Powder Formulation for Anti-Tuberculosis Drug Spectinamide 1599. / Stewart, Ian E.; Lukka, Pradeep B.; Liu, Jiuyu; Meibohm, Bernd; Gonzalez-Juarrero, Mercedes; Braunstein, Miriam S.; Lee, Richard E.; Hickey, Anthony J.

In: Pharmaceutical Research, Vol. 36, No. 9, 136, 01.09.2019.

Research output: Contribution to journalArticle

Stewart, IE, Lukka, PB, Liu, J, Meibohm, B, Gonzalez-Juarrero, M, Braunstein, MS, Lee, RE & Hickey, AJ 2019, 'Development and Characterization of a Dry Powder Formulation for Anti-Tuberculosis Drug Spectinamide 1599', Pharmaceutical Research, vol. 36, no. 9, 136. https://doi.org/10.1007/s11095-019-2666-8
Stewart, Ian E. ; Lukka, Pradeep B. ; Liu, Jiuyu ; Meibohm, Bernd ; Gonzalez-Juarrero, Mercedes ; Braunstein, Miriam S. ; Lee, Richard E. ; Hickey, Anthony J. / Development and Characterization of a Dry Powder Formulation for Anti-Tuberculosis Drug Spectinamide 1599. In: Pharmaceutical Research. 2019 ; Vol. 36, No. 9.
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