Formulation development of itraconazole PEGylated nano-lipid carriers for pulmonary aspergillosis using hot-melt extrusion technology

Gauri Shadambikar; Sushrut Marathe; Nan Ji; Mashan Almutairi; Suresh Bandari; Feng Zhang; Mahavir Chougule; Michael Repka

International Journal of Pharmaceutics: X (Dec 2021)

Formulation development of itraconazole PEGylated nano-lipid carriers for pulmonary aspergillosis using hot-melt extrusion technology

Gauri Shadambikar,
Sushrut Marathe,
Nan Ji,
Mashan Almutairi,
Suresh Bandari,
Feng Zhang,
Mahavir Chougule,
Michael Repka

Affiliations

Gauri Shadambikar: Department of Pharmaceutics and Drug Delivery, University of Mississippi, University, MS 38677, USA
Sushrut Marathe: Department of Pharmaceutics and Drug Delivery, University of Mississippi, University, MS 38677, USA
Nan Ji: Department of Pharmaceutics and Drug Delivery, University of Mississippi, University, MS 38677, USA
Mashan Almutairi: Department of Pharmaceutics and Drug Delivery, University of Mississippi, University, MS 38677, USA; Department of Pharmaceutics, College of Pharmacy, University of Hail, Hail 81442, Saudi Arabia
Suresh Bandari: Department of Pharmaceutics and Drug Delivery, University of Mississippi, University, MS 38677, USA
Feng Zhang: College of Pharmacy, The University of Texas at Austin, TX 78712, USA
Mahavir Chougule: Department of Pharmaceutics and Drug Delivery, University of Mississippi, University, MS 38677, USA
Michael Repka: Department of Pharmaceutics and Drug Delivery, University of Mississippi, University, MS 38677, USA; Pii Center for Pharmaceutical Technology, University of Mississippi, University, MS 38677, USA; Corresponding author at: Department of Pharmaceutics and Drug Delivery, Pii Center for Pharmaceutical Technology, School of Pharmacy, University of Mississippi, University, MS 38677, USA.

Journal volume & issue: Vol. 3
p. 100074

Abstract

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Pulmonary delivery is a promising alternative for the oral treatment of pulmonary aspergillosis. This study aimed to develop continuous and scalable itraconazole PEGylated nano-lipid carriers (ITZ-PEG-NLC) for inhalation delivery. The feasibility of preparing NLCs utilizing hot-melt extrusion (HME) coupled with probe sonication was investigated. The process parameters for HME and sonication were varied to optimize the formulation. ITZ-PEG-NLC (particle size, 101.20 ± 1.69 nm; polydispersity index, 0.26 ± 0.01) was successfully formulated. The drug entrapment efficiency of ITZ-PEG-NLC was 97.28 ± 0.50%. Transmission electron microscopy was used to characterize the shape of the particles. The developed formulations were evaluated for their aerodynamic properties for pulmonary delivery. The lung deposition of ITZ-PEG-NLC was determined using an Anderson Cascade Impactor and Philips Respironics Sami the Seal Nebulizer Compressor. In vitro cytotoxicity studies were performed using A549 cells. A burst-release pattern was observed in ITZ-PEG-NLC with a drug release of 41.74 ± 1.49% in 60 min. The in vitro aerosolization of the ITZ-PEG-NLC formulation showed a mass median aerodynamic diameter of 3.51 ± 0.28 μm and a geometric standard deviation of 2.44 ± 0.49. These findings indicate that HME technology could be used for the production of continuous scalable ITZ-PEG-NLC.

Published in International Journal of Pharmaceutics: X

ISSN: 2590-1567 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Pharmacy and materia medica
Website: https://www.journals.elsevier.com/international-journal-of-pharmaceutics-x

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