Evidence map›Paper›PMID 36114362›Full record

ArticlePharmaceutical research2022

Optimization and Scale Up of Spray Dried CPZEN-45 Aerosol Powders for Inhaled Tuberculosis Treatment.

Ian E Stewart, Phillip G Durham, Jacob M Sittenauer, Aranza P Barreda, Grayson W Stowell, Carmella Moody, Jeffery B Mecham, Catherine Simpson, Sharon Daily, Sara E Maloney and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Pharmaceutical research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.1field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 7 citations in OpenAlex.

  1. Outstanding Contributions to Aerosol Pulmonary Drug Delivery.Kona : powder science and technology in Japan · 2026
    Article
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  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

Ian E Stewart *Technology Advancement and Commercialization, RTI International, Durham, NC, USA.
Phillip G Durham *Department of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jacob M SittenauerCritiTech Particle Engineering Solutions, Lawrence, KS, USA.
Aranza P BarredaCritiTech Particle Engineering Solutions, Lawrence, KS, USA.
Grayson W StowellSocial, Statistical, and Environmental Sciences, RTI International, Durham, NC, USA.
Carmella MoodySocial, Statistical, and Environmental Sciences, RTI International, Durham, NC, USA.
Jeffery B MechamTechnology Advancement and Commercialization, RTI International, Durham, NC, USA.
Catherine SimpsonSocial, Statistical, and Environmental Sciences, RTI International, Durham, NC, USA.
Sharon DailySocial, Statistical, and Environmental Sciences, RTI International, Durham, NC, USA.
Sara E MaloneyTechnology Advancement and Commercialization, RTI International, Durham, NC, USA.
Mark D WilliamsCritiTech Particle Engineering Solutions, Lawrence, KS, USA.
Diana Severynse-StevensSocial, Statistical, and Environmental Sciences, RTI International, Durham, NC, USA.
Anthony J HickeyTechnology Advancement and Commercialization, RTI International, Durham, NC, USA. ahickey@rti.org.
RTI International · USCritiTech (United States) · USUniversity of North Carolina at Chapel Hill · US

Funding

Development of Inhaled CPZEN-45 For Tuberculosis TherapyR01AI141082 · NIAID · RESEARCH TRIANGLE INSTITUTE · PI SEVERYNSE-STEVENS, DIANA M · 2019 to 2022
$4.5M
Inhaled Caprazamycin for Tuberculolsis TherapyR01AI091882 · NIAID · RESEARCH TRIANGLE INSTITUTE · PI HICKEY, ANTHONY JAMES · 2011 to 2013
$957k
NIAID NIH HHS R01 AI091882NIAID NIH HHS R01 AI141082
6 · The paper itself

Abstract

purposeTuberculosis (TB) remains one of the most serious diseases caused by a single organism. Multiple (MDR) and extensively (XDR) drug resistant disease poses a threat to global health and requires new drugs and/or innovative approaches to treatment. A number of drugs have been proposed as inhaled therapy for TB, frequently prepared by spray drying. CPZEN-45 is a novel anti-tubercular drug that has poor oral bioavailability but has shown promise when administered via inhalation.

methodsExcipient-free CPZEN-45 HCl has been spray dried into a powder with physicochemical characteristics, aerodynamic particle size distribution, and delivered dose suitable for consideration as an inhaled product.

resultsThe mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of the powder delivered using a RS01 inhaler were 2.62 ± 0.04 μm and 1.76 ± 0.09, respectively. Additionally, the powder was physically and chemically stable after storage at ambient conditions for >1.5 years with particle size similar to freshly manufactured product. Overages in spray dried powder were recycled the powder and resprayed into drug product likewise resulting in negligible change in quality thus allowing for further preclinical characterization as necessary. CPZEN-45 was scaled up using pilot-scale manufacturing equipment where the density of the powder was increased to facilitate larger delivered doses without affecting the aerodynamic performance properties.

conclusionThe spray dried powders were suitable for pharmacokinetics, efficacy and preclinical toxicology studies. The final method of manufacture may be used directly for CGMP particle manufacture to support IND and Phase I clinical trials and beyond.

Indexed as

Aerosolized Particles and DropletsTuberculosisAdministration, InhalationAerosolsAzepinesDry Powder InhalersHumansParticle SizePowdersAerosolized Particles and DropletsAerosolsAzepinesCPZEN-45Powdersaerosolinhaled drugsscale-upspray dryingtuberculosis

Identifiers

PMID36114362
PMCPMC9483285
OpenAlexW4295997730

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.