cpzen-45 and Tuberculosis

cpzen-45 has been researched along with Tuberculosis* in 3 studies

Other Studies

3 other study(ies) available for cpzen-45 and Tuberculosis

ArticleYear
Optimization and Scale Up of Spray Dried CPZEN-45 Aerosol Powders for Inhaled Tuberculosis Treatment.
    Pharmaceutical research, 2022, Volume: 39, Issue:12

    Tuberculosis (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.. Excipient-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.. The 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.. The 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.

    Topics: Administration, Inhalation; Aerosolized Particles and Droplets; Aerosols; Dry Powder Inhalers; Humans; Particle Size; Powders; Tuberculosis

2022
A Spray-Dried Combination of Capreomycin and CPZEN-45 for Inhaled Tuberculosis Therapy.
    Journal of pharmaceutical sciences, 2019, Volume: 108, Issue:10

    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.

    Topics: Administration, Inhalation; Aerosols; Animals; Antibiotics, Antitubercular; Antitubercular Agents; Azepines; Capreomycin; Chemistry, Pharmaceutical; Dry Powder Inhalers; Guinea Pigs; Lung; Male; Particle Size; Powders; Tuberculosis

2019
Biopharmaceutical in vitro characterization of CPZEN-45, a drug candidate for inhalation therapy of tuberculosis.
    Therapeutic delivery, 2013, Volume: 4, Issue:8

    The caprazamycin derivative, CPZEN-45 has previously demonstrated antitubercular activity against Mycobacterium tuberculosis H37Rv. Here, the authors report a basic biopharmaceutical characterization of the compound focusing on in vitro permeability and cytotoxicity, with respect to the suitability of CPZEN-45 hydrochloride for inhalation treatment of tuberculosis.. MTT assays confirmed that CPZEN-45 HCl had no acute cytotoxic effects up to 3 mg/ml. In transport studies, apparent permeability coefficients of CPZEN-45 HCl across Calu-3 monolayers in absorptive and secretive directions were 0.43 ± 0.20 × 10(-6) cm/s and 0.38 ± 0.12 × 10(-6) cm/s, respectively. Across ATI-like monolayers, apparent permeability values were 12.10 ± 4.31 × 10(-6) cm/s and 8.50 ± 1.83 × 10(-6) cm/s. CPZEN-45 HCl formed colloidal complexes at concentrations above 0.38 mg/ml; however, these complexes were not micelles, as assessed by Orange OT encapsulation assay.. CPZEN-45 is an interesting new drug candidate with potential to be used in aerosol therapy of tuberculosis.

    Topics: Administration, Inhalation; Antitubercular Agents; Azepines; Cell Proliferation; Cells, Cultured; Humans; Micelles; Permeability; Tuberculosis

2013