A freeze-dried formulation of ivacaftor, ciprofloxacin, and L-salbutamol may be a novel approach to treating Pseudomonas aeruginosa infections and bronchoconstriction in patients with cystic fibrosis (CF), according to a new study published in DARU Journal of Pharmaceutical Sciences.
The researchers prepared the microparticles with bovine serum albumin and L-leucine using the freeze-drying approach. After optimizing the process and formulation parameters, they surface-coated the microparticles with L-salbutamol using the dry-blending method.
These microparticles were later examined in vitro for entrapment, inhalability, antimicrobial activity, cytotoxicity study, and safety. The study authors used the Anderson cascade impactor to assess the behavior of the microparticles when loaded into an inhaler.
According to the results, the size of the freeze-dried microparticles was 817.5±5.6 nm, the mass median aerodynamic diameter was 3.75±0.07 μm, and the geometric standard diameter was 1.66±0.033 μm. The particles had a polydispersity ratio of 0.33 and a zeta potential of −23.3±1.1 mV.
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Furthermore, the loading efficiency of the microparticles was good for all three drugs. Differential scanning calorimetry, scanning electron microscope, X-ray diffraction, and Fourier-transformed infrared spectroscopy studies confirmed the entrapment of ivacaftor and ciprofloxacin, while scanning electron microscope and transmission electron microscope scans described the shape and smooth surface of the particles.
Agar broth confirmed a good antimicrobial synergism of the formulation. According to the MTT assay, the dilution technique and the formulation appeared to have a favorable safety profile.
“The selected freeze-dried formulations showed desirable aerosolization properties,“ Kabra and Lahoti wrote. “The formulations also demonstrated superior drug distribution, and uptake studies demonstrated a much higher drug uptake and phagocytosis of ivacaftor in Calu-3 cell lines for the freeze-dried formulation.“
About 27% of patients with CF aged 2 to 5 years and 60% to 70% of adult patients are infected with P. aeruginosa and suffer persistent bronchospasm as a result.
Kabra VD, Lahoti SR. Novel therapeutic approach for the treatment of cystic fibrosis based on freeze-dried tridrug microparticles to treat cystic fibrosis. Daru. Published online May 4, 2023. doi:10.1007/s40199-023-00460-4