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Indian Journal of Pharmaceutical Education and ResearchNOW IN
Article

Inhalable Solubilized Zileuton for Improved Lung Targeting in vitro and in vivo Analysis

Afzal Haq Asif1★, Girish Meravanige2, Sreeharsha Nagaraja1,3, Arshia Shariff4, Juturu Thimmasetty5, Kavitha Arenur Narayana6★ Corresponding author

  1. 1Department of Pharmacy Practice, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, SAUDI ARABIA.
  2. 2Department of Biomedical Sciences, College of Medicine, King Faisal University, Al-Ahsa, SAUDI ARABIA.
  3. 3Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Hofuf, Al-Ahsa, SAUDI ARABIA.
  4. 4Department of Pharmaceutics, Vidya Siri College of Pharmacy, Bangalore, Karnataka, INDIA.
  5. 5Department of Pharmaceutics, Bapuji Pharmacy College, Davanagere, Karnataka, INDIA.
  6. 6Department of Pharmaceutical Quality Assurance, Krupanidhi College of Pharmacy, Bangalore, Karnataka, INDIA.

CORRESPONDENCE

Afzal Haq Asif

Department of Pharmacy Practice, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, 31982, SAUDI ARABIA.

ahasif@kfu.edu.sa

Received: 23-07-2022; Revised: 12-09-2022; Accepted: 28-11-2022.

Volume 57, Issue 2S · pp. s307–s314 · PUBLISHED 2023 · DOI: 10.5530/ijper.57.2s.35

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ABSTRACT

Background: Pulmonary diseases that affect the normal functioning of the lungs show airway symptoms ranging from change in airflow to bronchiectasis. Zileuton is an inhibitor of 5-lipoxygenase enzyme that catalyzes the synthesis of leukotrienes. Zileuton is used in the management of inflammatory conditions of the upper airways like obstructive pulmonary conditions and acute lung inflammation. Although a promising therapeutic, zileuton is poorly water-soluble and requires frequent administration to overcome bioavailability issues and maintain therapeutic levels that often lead to adverse reactions, especially to the non-targeted organs. Materials and Methods: Therefore, we designed a rapidly nanoemulsifying formulation of zileuton using Acrysol K150 as an oil, Cremophor EL as a surfactant, and Transcutol HP as a cosolvent. Results: This self-emulsifying composition exhibited showed a mean globule size of 133 ± 3.6 nm with a polydispersity index of 0.38. Scanning electron microscopy (SEM) images revealed the spherical shape of emulsion globules. In vitro lung deposition showed >80% delivery to the deep lung tissue. Mass median aerodynamic diameter of 2.05±0.98 μm for the aerosolized formulation. In vivo, pharmacokinetic studies in Wistar rats by inhalation route showed that the zileuton-loaded nanoemulsifying formulation had a significantly higher concentration in the lung compared to other non-target organs. The in vivo efficacy in the lipopolysaccharide-induced acute lung inflammation model in rats significantly impeded the protein accumulation and neutrophil infiltration in the lungs. Conclusion: The zileuton-loaded nanoemulsifying inhalable formulation successfully improved the therapeutic efficacy of zileuton specifically to the lung thereby minimizing the off-target organ side effects.

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    Asif, A. H., Meravanige, G., Nagaraja, S., Shariff, A., Thimmasetty, J., & Narayana, K. A. (2023). Inhalable Solubilized Zileuton for Improved Lung Targeting in vitro and in vivo Analysis. Indian Journal of Pharmaceutical Education and Research, 57(2S), s307–s314. https://doi.org/10.5530/ijper.57.2s.35