Naslov
In situ gelling fluticasone propionate nanosuspension: Quality by Design approach in the optimization of nasal delivery

Autori
Nižić Nodilo, Laura ; Perkušić, Mirna ; Špoljarić, Drago ; Ugrina, Ivo ; Amidžić Klarić, Daniela ; Pepić, Ivan ; Saršon, Vesna ; Safundžić Kučuk, Maša ; Zadravec, Dijana ; Kalogjera, Livije ; Hafner, Anita

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, ostalo, znanstveni

Skup
2021 CRS Virtual Annual Meeting

Mjesto i datum
Online skup, 25.07.2021. - 29.07.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
nasal drug delivery ; in situ gel ; nanoparticle suspension ; 3D printed nasal cast

Sažetak
Introduction: Nanosuspensions present innovative formulations with enhanced solubility and volume- controlled dissolution rate of poorly water- soluble drugs as well as improved particle mucoadhesive properties(1). Developing of in situ gelling systems presents the strategy to reduce the mucociliary clearance and extend the contact time between the drug and the nasal mucosa (2). In order to ensure targeted delivery of such systems, deposition studies should be implemented in early phase of formulation development (3). The aim of this study is to prepare in situ gelling fluticasone propionate (FP) nanosuspension with rheological properties suitable for nasal delivery and develop a regression model for nasal deposition pattern using Quality by Design(QbD) principles. Methods: QbD approach was employed in development of in situ gelling FP nanosuspensions prepared by wet media milling (1), with Tween 80 as a suspending agent, and pectin and sodium hyaluronate (SH) as mucoadhesive and/or in situ gelling polymers. The in situ gelling FP nanosuspensions were characterised in terms of particle size and zeta- potential, sprayability and rheological properties. Nasal deposition pattern was studied using 3D printed nasal cast connected to respiratory pump. Results: In situ gelling FP nanosuspensions (d=133.0–213.7 nm, PDI=0.227-0.386 ; zeta-potential=(-93.1) - (-77.2) mV) have been successfully prepared and showed suitable stability profile during 1-month storage at 4°C. They showed shear-thinning behaviour and instant gelation upon mixing with simulated nasal fluid. Regression modelling revealed Tween 80 concentration, SH concentration and interaction between FP and SH concentration to be the key factors determining sprayability of developed nanosuspensions. Formulation and administration parameters employed resulted in suitable range of droplet size distribution (Dv10=16.9-30.4 μm ; Dv50=38.7-100.7 μm ; Dv90=98.2- 219.3 μm) and spray cone angle (17.0-36.2°) ensuring targeted deposition within the nasal cavity. Conclusions/Impact: The formulation strategy employed showed the potential of coupling inherent advantages of nanosuspensions with benefits of shear-thinning in situ gelling platforms including appropriate sprayability, targeted deposition in the regions beyond the nasal valve and potential to ensure prolonged retention at the site of delivery. QbD approach enabled recognition of crucial parameters in formulation and nasal administration of in situ gelling FP nanosuspensions.

Izvorni jezik
Engleski

Znanstvena područja
Farmacija

POVEZANOST RADA