Capreomycin supergenerics for pulmonary tuberculosis treatment: preparation, in vitro, and in vivo characterization.

Abstract

The pulmonary route is one of the main strategies investigated to improve tuberculosis therapy. The aim of this study was to develop a simple and scalable method to produce capreomycin inhalable powders to use as supergeneric. In vitro antimycobacterial activity and in vivo acute toxicity were assessed using agar proportion susceptibility test on Mycobacterium tuberculosis and chicken chorioallantoic membrane assay, respectively. Capreomycin and three different hydrophobic counterions, namely oleate, linoleate, and linolenate, were combined in solution to obtain hydrophobic ion-pairs that were successively spray-dried. Ion-pairing efficiency was influenced by the spray-dryer employed to produce the powder. In the case of capreomycin oleate, both instruments, mini and nano spray-dryer, were suitable to maintain a high ion-paired content, while for capreomycin linoleate and linolenate, mini spray-dryer was the most appropriate instrument. The three formulations showed morphology and particle sizes potentially suitable for inhalation. Capreomycin oleate and linoleate showed the same efficacy of capreomycin sulfate against M. tuberculosis, while capreomycin linolenate showed a reduced efficacy, even though strain growth was inhibited at 10(-4) mycobacterial inoculum. In vivo acute toxicity studies evidenced the lowest toxic potential for capreomycin oleate when compared to the single components or the other two salts. Overall, capreomycin oleate seems to possess the most promising characteristics to be used as supergenerics in pulmonary tuberculosis treatment.

• Authors: Aurélie Schoubben, Paolo Blasi, Maria Luisa Marenzoni, Lanfranco Barberini, Stefano Giovagnoli, Carlo Cirotto, Maurizio Ricci
• Journal: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V (Eur J Pharm Biopharm) Vol. 83 Issue 3 Pg. 388-95 (Apr 2013) ISSN: 1873-3441 [Electronic] Netherlands
• PMID: 23220041 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Antitubercular Agents
• Powders
• Capreomycin

Topics

• Animals
• Antitubercular Agents (chemistry, therapeutic use)
• Capreomycin (chemistry, therapeutic use)
• Chick Embryo
• Humans
• In Vitro Techniques
• Microbial Sensitivity Tests
• Microscopy, Electron, Scanning
• Mycobacterium tuberculosis (drug effects)
• Powders
• Tuberculosis, Pulmonary (drug therapy, microbiology)