Unit:
Κατεύθυνση Βιομηχανική ΦαρμακευτικήLibrary of the School of Science
Author:
Zaromytidou-Zaromitidis Georgia
Supervisors info:
Δημήτριος Μ. Ρέκκας, Αναπληρωτής Καθηγητής του Τομέα Φαρμακευτικής Τεχνολογίας του Τμήματος Φαρμακευτικής του Εθνικού και Καποδιστριακού Πανεπιστημίου Αθηνών
Γεωργία Βαλσαμή, Αναπληρώτρια Καθηγήτρια του Τομέα Φαρμακευτικής Τεχνολογίας του Τμήματος Φαρμακευτικής του Εθνικού και Καποδιστριακού Πανεπιστημίου Αθηνών
Δάλλας Παρασκευάς, Επίκουρος Καθηγητής του Τομέα Φαρμακευτικής Τεχνολογίας του Τμήματος Φαρμακευτικής του Εθνικού και Καποδιστριακού Πανεπιστημίου Αθηνών
Original Title:
Development and in vitro evaluation of itraconazole dry powder for inhalation using experimental design
Translated title:
Development and in vitro evaluation of itraconazole dry powder for inhalation using experimental design
Summary:
With the significant morbidity and mortality rates due to pulmonary infectious diseases, there is an increasing interest in the antifungal pulmonary drug delivery. It seems to be a promising alternative, providing sufficiently high drug concentrations in the lung, improved bioavailability and reduced side effects. Itraconazole, due to its low aqueous solubility, entails the risk of the limited solubilization in the lung fluid and the subsequent impaired therapeutic effect. As possible deficiencies of the already applied methods, the complexity of the process and the subsequent cost-related concerns or the weak aerodynamic performance could be mentioned. Therefore, the aim of the present study was the development of a simple and non-organic solvent method for the formulation of itraconazole spray-dried powders for inhalation, characterized by improved aerodynamic properties.
Aqueous nanosuspensions containing drug and excipients with auxiliary role were produced through high speed and high pressure homogenization. Spray drying was used for the formation of engineered microparticles. The formulations were based on a 22 full-factorial experimental design generated using the software Design Expert® Version 11. The number of homogenization cycles (20, 40 and 60) and the Itz/Mannitol ratio (1:3, 1:1 and 3:1) were selected as the two factors under investigation. The particle size distribution analysis was carried out by laser diffraction methods whereas the in vitro aerodynamic assessment of spray-dried powders was performed using the Fast Screening Impactor (FSI) with RS01 dry powder inhaler (DPI) device and size 3 hard HPMC capsules.
Respirable powders containing itraconazole submicron particles were successfully developed without the use of organic solvents. All the experiments resulted in microparticles with geometric size favourable for an appropriate aerodynamic diameter (<5μm). The best emitted fractions (EF) (~80%) were assessed for the formulations with the low percentage of itraconazole. Nevertheless, all the formulations exhibited interestingly high Fine Particle Fractions (FPF) (>65%) and Fine particle Doses (FPD) (>2 mg). Consequently, the proposed formulation and process offer an advantageous approach for the development of highly respirable powders of itraconazole, emerging from a simple, less hazardous, environmental-friendly and scalable technique.
Main subject category:
Science
Other subject categories:
Health Sciences
Keywords:
Itraconazole, dry powder for inhalation, aqueous nanosuspension, high pressure homogenization, spray-drying, experimental design
Number of references:
139
File:
File access is restricted until 2025-06-01.
Master's thesis, GEORGIA ZAROMYTIDOU.pdf
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File access is restricted until 2025-06-01.
