Quality by Design Based Formulation Study of Meloxicam-Loaded Polymeric Micelles for Intranasal Administration
Our study aimed to develop an “ex tempore” reconstitutable, viscosity enhancer- and preservative-free meloxicam (MEL)-loaded polymeric micelle formulation, via Quality by Design (QbD) approach, exploiting the nose-to-brain pathway, as a suitable tool in the treatment of neuroinflammation. The anti-n...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-07-01
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| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/12/8/697 |
| _version_ | 1827712449030127616 |
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| author | Bence Sipos Piroska Szabó-Révész Ildikó Csóka Edina Pallagi Dorina Gabriella Dobó Péter Bélteky Zoltán Kónya Ágota Deák László Janovák Gábor Katona |
| author_facet | Bence Sipos Piroska Szabó-Révész Ildikó Csóka Edina Pallagi Dorina Gabriella Dobó Péter Bélteky Zoltán Kónya Ágota Deák László Janovák Gábor Katona |
| author_sort | Bence Sipos |
| collection | DOAJ |
| description | Our study aimed to develop an “ex tempore” reconstitutable, viscosity enhancer- and preservative-free meloxicam (MEL)-loaded polymeric micelle formulation, via Quality by Design (QbD) approach, exploiting the nose-to-brain pathway, as a suitable tool in the treatment of neuroinflammation. The anti-neuroinflammatory effect of nose-to-brain NSAID polymeric micelles was not studied previously, therefore its investigation is promising. Critical product parameters, encapsulation efficiency (89.4%), Z-average (101.22 ± 2.8 nm) and polydispersity index (0.149 ± 0.7) and zeta potential (−25.2 ± 0.4 mV) met the requirements of the intranasal drug delivery system (nanoDDS) and the targeted profile liquid formulation was transformed into a solid preservative-free product by freeze-drying. The viscosity (32.5 ± 0.28 mPas) and hypotonic osmolality (240 mOsmol/L) of the reconstituted formulation provides proper and enhanced absorption and probably guarantees the administration of the liquid dosage form (nasal drop and spray). The developed formulation resulted in more than 20 times faster MEL dissolution rate and five-fold higher nasal permeability compared to starting MEL. The prediction of IVIVC confirmed the great potential for in vivo brain distribution of MEL. The nose-to-brain delivery of NSAIDs such as MEL by means of nanoDDS as polymeric micelles offers an innovative opportunity to treat neuroinflammation more effectively. |
| first_indexed | 2024-03-10T18:15:01Z |
| format | Article |
| id | doaj.art-708a73b60fc44a44b9d31b018a3fd8c0 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T18:15:01Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-708a73b60fc44a44b9d31b018a3fd8c02023-11-20T07:48:46ZengMDPI AGPharmaceutics1999-49232020-07-0112869710.3390/pharmaceutics12080697Quality by Design Based Formulation Study of Meloxicam-Loaded Polymeric Micelles for Intranasal AdministrationBence Sipos0Piroska Szabó-Révész1Ildikó Csóka2Edina Pallagi3Dorina Gabriella Dobó4Péter Bélteky5Zoltán Kónya6Ágota Deák7László Janovák8Gábor Katona9Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, H-6720 Szeged, HungaryFaculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, H-6720 Szeged, HungaryFaculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, H-6720 Szeged, HungaryFaculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, H-6720 Szeged, HungaryFaculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, H-6720 Szeged, HungaryFaculty of Science and Informatics, Department of Applied & Environmental Chemistry, H-6720 Szeged, HungaryFaculty of Science and Informatics, Department of Applied & Environmental Chemistry, H-6720 Szeged, HungaryInterdisciplinary Excellence Centre, Department of Physical Chemistry and Materials Science, H-6720 Szeged, HungaryInterdisciplinary Excellence Centre, Department of Physical Chemistry and Materials Science, H-6720 Szeged, HungaryFaculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, H-6720 Szeged, HungaryOur study aimed to develop an “ex tempore” reconstitutable, viscosity enhancer- and preservative-free meloxicam (MEL)-loaded polymeric micelle formulation, via Quality by Design (QbD) approach, exploiting the nose-to-brain pathway, as a suitable tool in the treatment of neuroinflammation. The anti-neuroinflammatory effect of nose-to-brain NSAID polymeric micelles was not studied previously, therefore its investigation is promising. Critical product parameters, encapsulation efficiency (89.4%), Z-average (101.22 ± 2.8 nm) and polydispersity index (0.149 ± 0.7) and zeta potential (−25.2 ± 0.4 mV) met the requirements of the intranasal drug delivery system (nanoDDS) and the targeted profile liquid formulation was transformed into a solid preservative-free product by freeze-drying. The viscosity (32.5 ± 0.28 mPas) and hypotonic osmolality (240 mOsmol/L) of the reconstituted formulation provides proper and enhanced absorption and probably guarantees the administration of the liquid dosage form (nasal drop and spray). The developed formulation resulted in more than 20 times faster MEL dissolution rate and five-fold higher nasal permeability compared to starting MEL. The prediction of IVIVC confirmed the great potential for in vivo brain distribution of MEL. The nose-to-brain delivery of NSAIDs such as MEL by means of nanoDDS as polymeric micelles offers an innovative opportunity to treat neuroinflammation more effectively.https://www.mdpi.com/1999-4923/12/8/697NSAIDnanoDDSpolymeric micellequality by designpreformulation studyfreeze-drying |
| spellingShingle | Bence Sipos Piroska Szabó-Révész Ildikó Csóka Edina Pallagi Dorina Gabriella Dobó Péter Bélteky Zoltán Kónya Ágota Deák László Janovák Gábor Katona Quality by Design Based Formulation Study of Meloxicam-Loaded Polymeric Micelles for Intranasal Administration Pharmaceutics NSAID nanoDDS polymeric micelle quality by design preformulation study freeze-drying |
| title | Quality by Design Based Formulation Study of Meloxicam-Loaded Polymeric Micelles for Intranasal Administration |
| title_full | Quality by Design Based Formulation Study of Meloxicam-Loaded Polymeric Micelles for Intranasal Administration |
| title_fullStr | Quality by Design Based Formulation Study of Meloxicam-Loaded Polymeric Micelles for Intranasal Administration |
| title_full_unstemmed | Quality by Design Based Formulation Study of Meloxicam-Loaded Polymeric Micelles for Intranasal Administration |
| title_short | Quality by Design Based Formulation Study of Meloxicam-Loaded Polymeric Micelles for Intranasal Administration |
| title_sort | quality by design based formulation study of meloxicam loaded polymeric micelles for intranasal administration |
| topic | NSAID nanoDDS polymeric micelle quality by design preformulation study freeze-drying |
| url | https://www.mdpi.com/1999-4923/12/8/697 |
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