Prikladnost pulsirajućeg nebulizatora za nazalnu primjenu in situ gelirajućih nanosuspenzija flutikazonpropionata

master's thesis

• Title (english): Applicability of pulsating nebulisers in nasal drug delivery of in situ gelling fluticasone propionate nanosuspension
• Author: Ante Mrše
• Mentor: Anita Hafner (mentor)
• Committee member: Anita Hafner (predsjednik povjerenstva)
• Committee member: Dubravka Vitali Čepo (član povjerenstva)
• Committee member: Ivan Pepić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical technology); Zagreb
• Defense date and country: 2021-09-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Nebulizatori kao uređaji za pulmonalnu primjenu lijekova vrlo su prisutni u bolničkom liječenju bolesti
pluća. Zadnjih godina razvijaju se novi modeli nebulizatora kako bi im se proširila primjena na druge
indikacije te izvanbolničko liječenje. Jedan od novijih tipova nebulizatora je pulsirajući nebulizator.
Specifičan je po pulsiranju inače konstantnog mlaza aerosola. Uslijed pulsiranja, aerosol prodire duboko u
nosnu šupljinu, te zahvaća i teško dostupne paranazalne sinuse. Primjenjivost pulsirajućeg nebulizatora u
nazalnoj primjeni inovativnih terapijskih sustava još se treba istražiti.
Cilj ovog rada bio je pripraviti pseudoplastične in situ gelirajuće nanosuspenzije flutikazonpropionata te
ispitati prikladnost pulsirajućeg nebulizatora za njihovu nazalnu primjenu.
Uspješno su pripravljene in situ gelirajuće nanosuspenzije flutikazonpropionata (0,06 %, m/m) prikladne
veličine čestica lijeka i indeksa polidisperznosti, korištenjem polisorbata 80 (0,03 %, m/m) kao tvari za
močenje, natrijevog hijaluronata (0,05 %, m/m) kao konstitutivnog polimera te pektina (0,9 %, m/m) i gelan
gume (0,1%, m/m) ili ksantan gume (0,05 %, m/m) kao in situ gelirajućih polimera. Pripravljene in situ
gelirajuće nanosuspenzije flutikazonpropionata pokazale su pseudoplastično ponašanje. Pulsirajući
nebulizator osigurao je isporuku in situ gelirajućih nanosuspenzija flutikazonpropionata konstantnom
brzinom. Pri radu pulsirajućeg nebulizatora tijekom 20, 30 ili 45 sekundi postignuta je zadovoljavajuća
ujednačenost isporučene mase in situ gelirajućih suspenzija flutikazonpropionata odnosno zadovoljavajuća
ujednačenost doziranja, neovisno o vremenu predgrijavanja uređaja. Pri dostavi in situ gelirajućih
nanosuspenzija pulsirajućim nebulizatorom ostvareno je sveobuhvatno i ujednačeno odlaganje lijeka u
cijelom modelu nosne šupljine. Ostvarena je depozicija u značajno dubljim dijelovima turbinatnog područja
nego u slučaju klasične dostave nazalnim sprejem.
Između in situ gelirajućih nanosuspenzija flutikazonpropionata pripremljenih uz dodatak gelan gume ili
ksantan gume nije primijećena razlika u depoziciji pri primjeni pulsirajućim nebulizatorom te se stoga
smatraju jednako prikladnima za takvu primjenu.

Abstract (english)

Nebulizers are drug delivery devices most commonly used in hospital setting for the treatment of a variety
of pulmonary diseases. During the last few years new nebulizer models are being developed in order to
expand its use toward new treatment indications and outside the hospitals. One of the most recent types of
nebulizers is the pulsating nebulizer. Its unique property is that, instead of applying a constant pressure on
the nebulized aerosol, it adds pulsation to the aerosol stream. The addition of pulsation to the aerosol stream
results in a deeper penetration of the nasal cavity, including penetration into the hard to reach paranasal
sinuses. The applicability of pulsating nebulizators in nasal administration of innovative drug delivery
systems still needs to be investigated.
The aim of this study was to prepare pseudoplastic in situ gelling fluticasone propionate nanosuspensions
and explore the applicability of pulsating nebulizer for their nasal delivery.
In this study, in situ gelling fluticasone propionate (0,06 %, w/w) nanosuspensions with appropriate particle
size and polydispersity index were successfully prepared using polysorbate 80 (0,03 %, w/w) as a wetting
agent, sodium hyaluronate (0,05 %, w/w) as s constitutive polymer and pectin (0,9 %, m/m) and gellan gum
(0,1%, w/w) or xanthan gum (0,05 %, w/w) as in situ gelling polymer. Both in situ gelling nanosuspensions
showed pseudoplastic behaviour. Pulsating nebulisation provided drug delivery of the in situ gelling
fluticasone propionate nanosuspensions at a constant velocity. At the nebulizer operating time of 20, 30 or
45 seconds appropriate dosing uniformity was achieved, regardless of the preheating time of the nebulizer.
Pulsating nebulisation of in situ gelling fluticasone propionate nanosuspensions provided widespread and
uniform drug deposition over the whole nasal cavity model. Nebulised aerosol reached much deeper parts
of the turbinate region in relation to the same nanosuspensions delivered by conventional nasal spray.
No significant difference was noticed between in situ gelling fluticasone propionate nanosuspensions
containing gellan gum or xanthan gum while being administrated with pulsating nebulizer and are therefore
considered equally suitable for this mode of nasal delivery.

• Keywords: nebulizator; nazalna primjena; in situ gelirajuće nanosuspenzije; flutikazonpropionat; gelan guma; ksantan guma
• Keywords (english): nebulizer; nasal drug delivery; in situ gelling nanosuspensions; fluticasone propionate; gellan gum; xanthan gum
• Language: croatian
• URN:NBN: urn:nbn:hr:163:712055
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-02-10 16:39:51