Projects of the Faculty of Pharmacy and Biochemistry
Optimisation of nasal deposition pattern of sprayable in situ gelling and powder drug delivery systems
| Status | Finished |
|---|---|
| Acronym | OptiNasalSpray |
| Summary | Nasal delivery receives much attention of the worldwide scientific community as an attractive route of administration for drugs with local or systemic effect, and especially neurological drugs that can be delivered directly from the nasal cavity to the brain. For all these aspects of nasal drug administration, different innovative drug delivery systems are being developed with the aim to enhance drug bioavailability at the site of action while minimizing the possibility for their adverse effects. Special efforts are made to develop technological platforms able to potentiate direct nose to brain delivery of neurologically acting drugs, as success in this investigation area would represent a turning point in the treatment of neurological diseases. The anatomy and physiology of the nasal cavity are recognized as the most critical factors in drug delivery system design, especially mucociliary apparatus/clearance that limits the contact time between the drug and the mucosal surface. However, the crucial parameter for the treatment outcome of nasally applied drug is its deposition within the nasal cavity. Despite the numerous literature reports on total formulation deposition within the nasal cavity, data on fractional deposition in different nasal regions (i.e. deposition pattern) are scarce, eventhough they are more clinically relevant for the prediction of therapeutic outcomes. The deposition pattern is influenced by the properties of nasal formulation and method of its administration, which can be fine-tuned with the aim to accomplish improved therapeutic efficiency. The purpose of the proposed project is to develop sprayable nasal delivery systems with carefully designed deposition pattern and favourable biopharmaceutical properties, in relation to targeted drug effect. Two model drugs will be used, namely, fluticasone - a locally acting drug that needs to reach the polyp zone beyond the nasal valve, and donepezil - antidementic drug that needs to be deposited in the olfactory region within the nasal cavity to be directly transported to the brain. For the formulation development, applicability of two pharmaceutical technologies/approaches that can be easily scaled up to an industrial-scale processing, will be assessed and compared, namely, development of in situ gelling systems and dry powder preparation by spray-drying. These technological platforms can be used to develop delivery systems able to prolong residence time at the site of deposition and control drug release and absorption profile, baring the potential to optimise pharmacokinetic profile of nasally administered drugs. Nasal deposition will be studied using nasal cavity model allowing simulation of breath airflow. The deposition pattern will be optimised by varying process and formulation parameters, in conjunction with different nasal devices and administration techniques (angle of administration and inhalation flow rate). The appropriate usage of the theory behind Statistical Design of Experiments, a core component of Quality-by-design approach, will enable the evaluation and elucidation of the influence of the formulation, process and administration parameters on the characteristics/deposition pattern of developed in situ gelling systems and spray-dried powders. Such an approach will potentiate the development of nasal formulations with built-in quality attributes in a cost and time-saving manner. Among the leading formulations, the oneHafner Application Form OptiNasalSpray with the highest therapeutic potential will be recognised based on the additional biopharmaceutical characterisation, i.e. in vitro biocompatibility and permeability studies. The systematic and overall approach to the development of the nasal sprayable systems proposed within this project will result in a proof-of-concept platform which can serve as a starting point/basis for upcoming investigations in the same research field. Providing deeper insight into the relationship between formulation, process and administration parameters, and nasal deposition pattern, represents the unique contribution of the proposed project. |
| Line of financing |
Croatian Science Foundation |
| Duration | 01.01.2018. - 31.03.2023. |
| Budget amount | 238.183,00 EUR |
| Lead | - |
| Results |
Tin Rogina, Freeze-drying of melatonin nanosuspension in the presence of a cryoprotectant, 2024, diploma thesis, University of Zagreb Faculty of Pharmacy and Biochemisty
Ivana Potočki, Influence of chitosan molecular weight on the properties of spray-dried donepezil-loaded microspheres, 2022., Diploma Thesis, University of Zagreb Faculty of Pharmacy and Biochemistry
Perkušić M, Nižić Nodilo L, Ugrina I, Špoljarić D, Jakobušić Brala C, Pepić I, Lovrić J, Safundžić Kučuk M, Trenkel M, Scherließ R, Zadravec D, Kalogjera L, Hafner A. Chitosan-Based Thermogelling System for Nose-to-Brain Donepezil Delivery: Optimising Formulation Properties and Nasal Deposition Profile. Pharmaceutics. 2023 Jun 5;15(6):1660. doi: 10.3390/pharmaceutics15061660. PMID: 37376108.
Pina Costa C, Nižić Nodilo L, Silva R, Martins E, Zadravec D, Kalogjera L, Nuno Moreira J, Manuel Sousa Lobo J, Hafner A, Catarina Silva A. In situ hydrogel containing diazepam-loaded nanostructured lipid carriers (DZP-NLC) for nose-to-brain delivery: development, characterization and deposition studies in a 3D-printed human nasal cavity model. Int J Pharm. 2023;644:123345. doi: 10.1016/j.ijpharm.2023.123345. Epub 2023 Aug 22. PMID: 37619806.
Nižić Nodilo L, Perkušić M, Ugrina I, Špoljarić D, Jakobušić Brala C, Amidžić Klarić D, Lovrić J, Saršon V, Safundžić Kučuk M, Zadravec D, Kalogjera L, Pepić I, Hafner A. In situ gelling nanosuspension as an advanced platform for fluticasone propionate nasal delivery. Eur J Pharm Biopharm. 2022 Jun;175:27-42. doi: 10.1016/j.ejpb.2022.04.009. Epub 2022 Apr 27. PMID: 35489667.
Nižić Nodilo L, Ugrina I, Špoljarić, D, Amidžić Klarić D, Jakobušić Brala C, Perkušić M, Pepić I, Lovrić J, Saršon V, Safundžić Kučuk M, Zadravec D, Kalogjera L, Hafner A. A Dry Powder Platform for Nose-to-Brain Delivery of Dexamethasone: Formulation Development and Nasal Deposition Studies. Pharmaceutics 2021, 13, 795. https://doi.org/10.3390/pharmaceutics13060795.
Perkušić M, Nižić Nodilo L, Ugrina I, Špoljarić D, Jakobušić Brala C, Pepić I, Lovrić J, Matijašić G, Gretić M, Zadravec D, Kalogjera L, Hafner A. Tailoring functional spray-dried powder platform for efficient donepezil nose-to-brain delivery. Int J Pharm. 2022 Aug 25;624:122038. doi: 10.1016/j.ijpharm.2022.122038. Epub 2022 Jul 20. PMID: 35870666.
Nižić L, Potaś J, Winnicka K, Szekalska M, Erak I, Gretić M, Jug M, Hafner A. Development, characterisation and nasal deposition of melatonin-loaded pectin/hypromellose microspheres. European Journal of Pharmaceutical Sciences, 2020,141:105-115. doi: 10.1016/j.ejps.2019.105115.
Nižić L, Ugrina I, Špoljarić D, Saršon V, Kučuk MS, Pepić I, Hafner A. Innovative sprayable in situ gelling fluticasone suspension: Development and optimization of nasal deposition. International Journal of Pharmaceutics, 2019, 563: 445-456. doi:10.1016/j.ijpharm.2019.04.015.
Mirna Perkušić, Laura Nižić Nodilo, Cvijeta Jakobušić Brala, Ivan Pepić, Jasmina Lovrić, Anita Hafner, Biopharmaceutical properties of mucoadhesive powder platform for donepezil nasal delivery. 80th FIP World Congress of Pharmacy and Pharmaceutical Sciences, Seville, Spain, September 18-22, 2022
Mirna Perkušić, Laura Nižić Nodilo, Ivo Ugrina, Drago Špoljarić, Cvijeta Jakobušić Brala, Ivan Pepić, Dijana Zadravec, Livije Kalogjera, Anita Hafner, Development of nasal donepezil powder platform employing statistical design. FIGON&EUFEPS European Medicines Days 2022, Leiden, Netherlands, June 1-3, 2022
Cláudia Pina Costa, Laura Nižić Nodilo, Dijana Zadravec, Livije Kalogjera, João Nuno Moreira, José Manuel Sousa Lobo, Anita Hafner and Ana Catarina Silva, Evaluation of the deposition of an in situ hydrogel containing diazepam loaded nanostructured lipid carriers (NLC) in a 3D nasal cavity mode. 13th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, Rotterdam, Netherlands, March 28-31, 2022
Mirna Perkušić, Laura Nižić Nodilo, Cvijeta Jakobušić Brala, Ivan Pepić, Dijana Zadravec, Livije Kalogjera, Vesna Saršon, Maša Safundžić Kučuk, Anita Hafner, Development of sprayable in situ gelling system for nasal donepezil delivery: preliminary formulation and deposition studies. 80th FIP World Congress of Pharmacy and Pharmaceutical Sciences, Seville, Spain, September 18-22, 2022
Laura Nižić Nodilo, Mirna Perkušić, Anita Hafner, OptiNasalSpray – Optimisation of Nasal Deposition Pattern of Sprayable In Situ Gelling and Powder Drug Delivery Systems. 1st Annual Korea-Croatia Conference on Lipid Membrane Biotechnology and Drug Delivery Applications (online symposium), November 22, 2021
Antonija Tržić, Suitability of donepezil-loaded chitosan-based in situ gelling system for nasal administration in the form of spray, 2024, Diploma Thesis, University of Zagreb Faculty of Pharmacy and Biochemistry
Tea Dvorski, Influence of the inlet temperature on the properties of the spray-dried donepezil-loaded microspheres, 2022., Diploma Thesis, University of Zagreb Faculty of Pharmacy and Biochemistry
Tamara Topalović, In vitro evaluation of nasal deposition of donepezil-loaded microspheres, 2022, Diploma Thesis, University of Zagreb Faculty of Pharmacy and Biochemistry
Laura Nižić, Ivo Ugrina, Drago Špoljarić, Vesna Saršon, Maša Safundžić Kučuk, Ivan Pepić, Anita Hafner, Optimisation of nasal deposition pattern of in situ gelling fluticasone suspension. 6. Hrvatski kongres farmacije s međunarodnim sudjelovanjem, Dubrovnik, Hrvatska, 04.04.2019.-07.04.2019.
Laura Nižić Nodilo, Mirna Perkušić, Cvijeta Jakobušić Brala, Daniela Amidžić Klarić, Ivan Pepić, Jasmina Lovrić, Dijana Zadravec, Livije Kalogjera, Anita Hafner, Mucoadhesive in situ gelling fluticasone propionate nanosuspension for nasal delivery by nebulization. 13th Central European Symposium on Pharmaceutical Technology, Gdansk, Polland, September 16-18, 2021
Laura Nižić Nodilo, Mirna Perkušić, Drago Špoljarić, Ivo Ugrina, Daniela Amidžić Klarić, Ivan Pepić, Vesna Saršon, Maša Safundžić Kučuk, Dijana Zadravec, Livije Kalogjera, Anita Hafner, In situ gelling fluticasone propionate nanosuspension: Quality by Design approach in the optimization of nasal delivery. Controlled Release Society 2021 Virtual Annual Meeting, July, 25-29, 2021
Laura Nižić Nodilo, Drago Špoljarić, Ivo Ugrina, Daniela Amidžić Klarić, Cvijeta Jakobušić Brala, Mirna Perkušić, Ivan Pepić, Jasmina Lovrić, Vesna Saršon, Maša Safundžić Kučuk, Dijana Zadravec, Livije Kalogjera, Anita Hafner, Development and in vitro evaluation of dry powder platform for nose-to-brain delivery of dexamethasone. Controlled Release Society 2021 Virtual Annual Meeting, July, 25-29, 2021
Veronika Ria Tus, Development of in situ gelling melatonin nanosuspension for nasal administration, 2023., Diploma Thesis, University of Zagreb Faculty of Pharmacy and Biochemistry
Laura Nižić, Ivan Pepić, Vesna Saršon Beltrame, Maša Safundžić Kučuk, Anita Hafner;Formulation and administration parameters for the optimisation of nasal deposition pattern of sprayable in situ gelling fluticasone delivery system. 12th Central European Symposium on Pharmaceutical Technology and Regulatory Affairs, Szeged, Hungary, Spetember 20-22, 2018 - (best poster award)
Maja Brozović, Ante Mrše, Laura Nižić, Ivan Pepić, Vesna Saršon, Maša Safundžić Kučuk, Anita Hafner, Sprayable in situ gelling fluticasone suspensions: nasal deposition upon bi-directional delivery in vitro. 2019 UKICRS Symposium, Liverpool, UK, June 3-4, 2019
Mirna Perkušić, Laura Nižić Nodilo, Gordana Matijašić, Marie Trenkel, Cord Kühnl, Regina Scherließ, Anita Hafner, Development of powder nasal forms for donepezil hydrochloride: assessment of nasal discomfort by mucosal irritation assay. 7th International Conference on Pharmaceutics and Advanced Drug Delivery Systems, London, UK, March 27-29, 2023
Laura Nižić Nodilo, Mirna Perkušić, Cvijeta Jakobušić Brala, Daniela Amidžić Klarić, Ivan Pepić, Jasmina Lovrić, Dijana Zadravec, Livije Kalogjera, Anita Hafner, Development of powder nasal forms for donepezil hydrochloride: formulation parameters impact. 13th Central European Symposium on Pharmaceutical Technology, Gdansk, Polland, September 16-18, 2021
Mirna Perkušić, Laura Nižić Nodilo, Ivo Ugrina, Drago Špoljarić, Cvijeta Jakobušić Brala, Ivan Pepić, Gordana Matijašić, Matija Gretić, Anita Hafner, Preparation of spray dried nasal donepezil powder platform using an ultrasonic nozzle. FIGON&EUFEPS European Medicines Days 2022, Leiden, Netherlands, June 1-3, 2022 (best poster award)
Anita Hafner, Development of innovative nasal drug delivery systems: example of academia-industry collaboration. Winter School of Research Commercialisation 2020; November, 24-28, 2020
Invited lecture: Razmatranja pri razvoju in situ gelirajućeg terapijskog sustava za nazalnu primjenuAnita Hafner, Razmatranja pri razvoju in situ gelirajućeg terapijskog sustava za nazalnu primjenu. 6. Hrvatski kongres farmacije s međunarodnim sudjelovanjem, Dubrovnik, Hrvatska, April 4-7, 2019
Mirna Perkušić, Development of advanced in situ gelling systems for nasal donepezil delivery, PhD Thesis, Zagreb, University of Zagreb Faculty of Pharmacy and Biochemistry, 2023.
Laura Nižić Nodilo, Development and nasal deposition optimisation of innovative pharmaceutical forms of corticosteroids, PhD Thesis, Zagreb, University of Zagreb Faculty of Pharmacy and Biochemistry, 2022
Maja Brozović, Ante Mrše, Nasal deposition of in situ gelling fluticasone propionate suspensions upon bidirectional delivery in vitro. Student research work awarded by Rector's award in academic year 2018/2019
Stefanie Bobičanec, Mia Kobaš, Dexamethasone-loaded microspheres blended with inert powder carrier: characterisation of pharmaceutical formulation and deposition within silicone nasal cavity model. Student research work awarded with Rector's award in academic year 2019/2020
Iva Šimović, In vitro characterisation of nasal powder delivery system of sodium dexamethasone phosphate using Calu-3 respiratory epithelial cell model, 2022, Diploma Thesis, University of Zagreb Faculty of Pharmacy and Biochemistry
Sara Blažon, Investigation of the effect of lactose and mannitol on nasal powder delivery system of sodium dexamethasone phosphate 2021, Diploma Thesis, University of Zagreb Faculty of Pharmacy and Biochemistry
David Horvat, Physicochemical characterization of fluticasone propionate in situ gelling nanosuspension for nasal delivery, 2021, Diploma Thesis, University of Zagreb Faculty of Pharmacy and Biochemistry
Ante Mrše, Applicability of pulsating nebulisers in nasal drug delivery of in situ gelling fluticasone propionate nanosuspension, 2021, Diploma Thesis, University of Zagreb Faculty of Pharmacy and Biochemistry
Julia Ružić, In vitro characterization of polymer microspheres for dexamethasone nasal delivery, 2020, Diploma Thesis, University of Zagreb Faculty of Pharmacy and Biochemistry
Stefanie Bobičanec, Biopharmaceutical characterisation of in situ gelling fluticasone propionate delivery system using Calu-3-epithelial cell model, 2020, Diploma Thesis, University of Zagreb Faculty of Pharmacy and Biochemistry
Patricia Dolanjski, Preparation of spray dried microspheres with sodium dexamethasone phosphate: impact of the feed composition and flow rate, 2020, Diploma Thesis, University of Zagreb Faculty of Pharmacy and Biochemistry
Mateja Pačarić, Pectin and hypromellose based microspheres for nasal delivery of dexamethasone sodium phosphate, 2020, Diploma Thesis, University of Zagreb Faculty of Pharmacy and Biochemistry
Maja Brozović, Rheological characterisation of nasal in situ gels with fluticasone propionate, 2019, Diploma Thesis, University of Zagreb Faculty of Pharmacy and Biochemistry
Emily Ćurt, Development of in situ gelling fluticasone propionate suspension for nasal administration, 2019, Diploma Thesis, University of Zagreb Faculty of Pharmacy and Biochemistry
Antonia Barišić, Applicability of pectin and hypromellose in the preparation of microspheres for fluticasone propionate nasal delivery, 2019, Diploma Thesis, University of Zagreb Faculty of Pharmacy and Biochemistry
Lucija Zečević, Development of in situ gelling pectin system as nasal drug delivery platform, 2018, Diploma Thesis, University of Zagreb Faculty of Pharmacy and Biochemistry
Mia Kobaš, Suitability assessment of selected cyclodextrins as solubilizers in fluticasone propionate in vitro permeation studies, 2020., Diploma Thesis, University of Zagreb Faculty of Pharmacy and Biochemistry
Ana Bano, Preparation and characterization of fluticasone propionate nanocrystals, 2019, Diploma Thesis, University of Zagreb Faculty of Pharmacy and Biochemistry
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