A Spray-Dried Combination of Capreomycin and CPZEN-45 for Inhaled Tuberculosis Therapy.

Autor:	Pitner RA; PAI Life Sciences, Seattle, Washington 98102; Department of Immunology, University of Washington School of Medicine, Seattle, Washington 98109., Durham PG; RTI International, Research Triangle Park, North Carolina 27709; Department of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599., Stewart IE; RTI International, Research Triangle Park, North Carolina 27709., Reed SG; Infectious Disease Research Institute (IDRI), Seattle, Washington 98102., Cassell GH; Infectious Disease Research Institute (IDRI), Seattle, Washington 98102., Hickey AJ; RTI International, Research Triangle Park, North Carolina 27709; Department of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599., Carter D; PAI Life Sciences, Seattle, Washington 98102; Infectious Disease Research Institute (IDRI), Seattle, Washington 98102. Electronic address: darrick.carter@pailifesciences.com.
Jazyk:	angličtina
Zdroj:	Journal of pharmaceutical sciences [J Pharm Sci] 2019 Oct; Vol. 108 (10), pp. 3302-3311. Date of Electronic Publication: 2019 May 29.
DOI:	10.1016/j.xphs.2019.05.024
Abstrakt:	Tuberculosis (TB) remains the single most serious infectious disease attributable to a single-causative organism. A variety of drugs have been evaluated for pulmonary delivery as dry powders: capreomycin sulfate has shown efficacy and was safely delivered by inhalation at high doses to human volunteers, whereas CPZEN-45 is a new drug that has also been shown to kill resistant TB. The studies here combine these drugs-acting by different mechanisms-as components of single particles by spray-drying, yielding a new combination drug therapy. The spray-dried combination powder was prepared in an aerodynamic particle size range suitable for pulmonary delivery. Physicochemical storage stability was demonstrated for a period of 6 months. The spray-dried combination powders of capreomycin and CPZEN-45 have only moderate affinity for mucin, indicating that delivered drug will not be bound by these mucins in the lung and available for microbicidal effects. The pharmacokinetics of disposition in guinea pigs demonstrated high local concentrations of drug following direct administration to the lungs and subsequent systemic bioavailability. Further studies are required to demonstrate the in vivo efficacy of the combination to confirm the therapeutic potential of this novel combination. (Copyright © 2019 American Pharmacists Association®. All rights reserved.)
Databáze:	MEDLINE
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