engleski

Optimisation of nasal deposition pattern of in situ gelling fluticasone suspension

Aim of the study The aim of this study is to develop regression model for nasal deposition pattern of in situ gelling fluticasone suspension. The fine tuning of formulation and administration parameters will be accomplished by employing Quality by Design principles that will enable elucidating and understanding of their impact on the plume geometry and deposition pattern. Materials and methods Fluticasone propionate (Carbosynth Ltd., UK), pectin (Herbstreith&Fox, Germany), gellan gum (Sigma-Aldrich, USA), sodium hyaluronate (Contipro, Czech Republic), Tween 80 (Sigma- Aldrich, USA) and mannitol (BDH Prolabo, UK) were used for the preparation of in situ gelling suspensions. The influence of formulation (fluticasone propionate, pectin, gellan-gum, sodium hyaluronate and Tween 80 concentration) and administration parameters (angle of administration from the horizontal plane and inhalation flow rate) on the plume geometry and nasal deposition pattern were investigated. Spray plume angle was measured by a virtual protractor after spraying against a dark background. Nasal deposition pattern was determined using nasal cavity model (Koken. Co. Ltd., Japan) and Sar-gel as water indicating paste (Sartomer Company Inc., USA). Respiratory pump (Harvard Apparatus, USA) was used to simulate inhalation. After actuation (Pump 3K, 140 μl, Aeropump, Germany), the spray and the Sar-gel were weighed to determine spray deposition. Results Spray cone angle of the in situ gelling formulations ranged between 26.9° and 57.4°. Spray cone angle decreased with the increase in polymer concentration. The effect of polymer concentration increased in the order: pectin˂gellan gum˂sodium hyaluronate. Fraction of the sprayed dose deposited in the turbinate region ranged between 0 and 98.8 %, showing the dependence on both, administration and formulation parameters, as well as their interactions. Decrease in the angle of administration from horizontal plane and increase in respiratory flow significantly increased the deposition in the turbinate region. The addition of sodium hyaluronate resulted in increase in turbinate deposition. The parameters in interactions include concentration of polymers, surfactant and fluticasone, as well as administration angle. Conclusion This study revealed formulation and/or administration parameters with significant influence on the plume geometry and deposition pattern of the in situ gelling fluticasone suspension. Predictive power of regression model obtained for plume geometry and deposition pattern enables the development of fluticasone in situ gelling suspension with built-in quality, maximizing cost and time savings. ACKNOWLEDGEMENTS This work has been supported in part by Croatian Science Foundation under the project UIP-2017- 05-4592.

Fluticasone ; Pectin ; Gellan gum ; Sodium hyaluronate ; In situ gelling ; Nasal deposition ; Quality by Design

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