The Effect of High-Pressure Homogenization Conditions on the Physicochemical Properties and Stability of Designed Fluconazole-Loaded Ocular Nanoemulsions
The growing interest in high-energy emulsification is a result of its scalability, which is important from an industrial perspective and allows for a more reproducible and efficient production of pharmaceutical formulations. The aim of this study was to evaluate the effect of composition, mainly a f...
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| Format: | Article |
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MDPI AG
2023-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/16/1/11 |
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| author | Agnieszka Gawin-Mikołajewicz Urszula Nawrot Katarzyna Hanna Malec Karolina Krajewska Karol Przemysław Nartowski Bożena Lucyna Karolewicz |
| author_facet | Agnieszka Gawin-Mikołajewicz Urszula Nawrot Katarzyna Hanna Malec Karolina Krajewska Karol Przemysław Nartowski Bożena Lucyna Karolewicz |
| author_sort | Agnieszka Gawin-Mikołajewicz |
| collection | DOAJ |
| description | The growing interest in high-energy emulsification is a result of its scalability, which is important from an industrial perspective and allows for a more reproducible and efficient production of pharmaceutical formulations. The aim of this study was to evaluate the effect of composition, mainly a fixed surfactant/cosurfactant (S<sub>mix</sub>) ratio, their concentration, and the parameters of high-pressure homogenization (HPH) processing on the quality and stability of ophthalmic fluconazole-loaded nanoemulsions. After a physicochemical analysis of nanoemulsions containing 20% <i>w</i>/<i>w</i> of oil, as optimal conditions for the HPH process, three cycles at a pressure of 1000 bar were established, obtaining formulations with an average droplet diameter size in the range of 80.63–129.68 nm and PDI values below 0.25. While it was expected that an increasing cosurfactant concentration decreased the droplet size, in the case of formulations containing Tween 20 and 10% <i>w</i>/<i>w</i> of cosurfactants, “over-processing” was observed, identified by the droplet size and polydispersity index increase. Consecutively, the selected formulations were evaluated for in vitro drug release in Franz’s cell, antifungal activity, and 30-day stability using NMR spectroscopy. An antifungal activity test showed no significant difference in the antifungal activity between optimal fluconazole-loaded nanoemulsions and a 0.3% aqueous drug solution, but previously, research showed that prepared formulations were characterized by a higher viscosity and satisfactory prolonged release compared to a control. In a 30-day stability study, it was observed that higher HLB values of the used surfactants decreased the stability of the formulations in the following order: Kolliphor EL, Tween 80, Tween 20. The NMR spectra confirmed that Kolliphor EL-based formulations ensured the higher stability of the nanoemulsion composition in comparison to Tween 80 and a better stabilizing effect of propylene glycol as a cosurfactant in comparison to PEG 200. Therefore, the optimization of HPH technology should be focused on the selection of S<sub>mix</sub> and the S<sub>mix</sub>:oil ratio in order to prepare stable formulations of high quality. |
| first_indexed | 2024-03-08T10:38:28Z |
| format | Article |
| id | doaj.art-7bcf0e26eceb4565a4356b6055bc1cfb |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-08T10:38:28Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-7bcf0e26eceb4565a4356b6055bc1cfb2024-01-26T18:06:15ZengMDPI AGPharmaceutics1999-49232023-12-011611110.3390/pharmaceutics16010011The Effect of High-Pressure Homogenization Conditions on the Physicochemical Properties and Stability of Designed Fluconazole-Loaded Ocular NanoemulsionsAgnieszka Gawin-Mikołajewicz0Urszula Nawrot1Katarzyna Hanna Malec2Karolina Krajewska3Karol Przemysław Nartowski4Bożena Lucyna Karolewicz5Department of Drug Form Technology, Wroclaw Medical University, 211A Borowska Str., 50-556 Wroclaw, PolandDepartment of Pharmaceutical Microbiology and Parasitology, Wroclaw Medical University, 211A Borowska Str., 50-556 Wroclaw, PolandDepartment of Drug Form Technology, Wroclaw Medical University, 211A Borowska Str., 50-556 Wroclaw, PolandDepartment of Drug Form Technology, Wroclaw Medical University, 211A Borowska Str., 50-556 Wroclaw, PolandDepartment of Drug Form Technology, Wroclaw Medical University, 211A Borowska Str., 50-556 Wroclaw, PolandDepartment of Drug Form Technology, Wroclaw Medical University, 211A Borowska Str., 50-556 Wroclaw, PolandThe growing interest in high-energy emulsification is a result of its scalability, which is important from an industrial perspective and allows for a more reproducible and efficient production of pharmaceutical formulations. The aim of this study was to evaluate the effect of composition, mainly a fixed surfactant/cosurfactant (S<sub>mix</sub>) ratio, their concentration, and the parameters of high-pressure homogenization (HPH) processing on the quality and stability of ophthalmic fluconazole-loaded nanoemulsions. After a physicochemical analysis of nanoemulsions containing 20% <i>w</i>/<i>w</i> of oil, as optimal conditions for the HPH process, three cycles at a pressure of 1000 bar were established, obtaining formulations with an average droplet diameter size in the range of 80.63–129.68 nm and PDI values below 0.25. While it was expected that an increasing cosurfactant concentration decreased the droplet size, in the case of formulations containing Tween 20 and 10% <i>w</i>/<i>w</i> of cosurfactants, “over-processing” was observed, identified by the droplet size and polydispersity index increase. Consecutively, the selected formulations were evaluated for in vitro drug release in Franz’s cell, antifungal activity, and 30-day stability using NMR spectroscopy. An antifungal activity test showed no significant difference in the antifungal activity between optimal fluconazole-loaded nanoemulsions and a 0.3% aqueous drug solution, but previously, research showed that prepared formulations were characterized by a higher viscosity and satisfactory prolonged release compared to a control. In a 30-day stability study, it was observed that higher HLB values of the used surfactants decreased the stability of the formulations in the following order: Kolliphor EL, Tween 80, Tween 20. The NMR spectra confirmed that Kolliphor EL-based formulations ensured the higher stability of the nanoemulsion composition in comparison to Tween 80 and a better stabilizing effect of propylene glycol as a cosurfactant in comparison to PEG 200. Therefore, the optimization of HPH technology should be focused on the selection of S<sub>mix</sub> and the S<sub>mix</sub>:oil ratio in order to prepare stable formulations of high quality.https://www.mdpi.com/1999-4923/16/1/11drug deliverysurfactantsocular nanoemulsionhigh-energy methodsprocess parametersformulation optimization |
| spellingShingle | Agnieszka Gawin-Mikołajewicz Urszula Nawrot Katarzyna Hanna Malec Karolina Krajewska Karol Przemysław Nartowski Bożena Lucyna Karolewicz The Effect of High-Pressure Homogenization Conditions on the Physicochemical Properties and Stability of Designed Fluconazole-Loaded Ocular Nanoemulsions Pharmaceutics drug delivery surfactants ocular nanoemulsion high-energy methods process parameters formulation optimization |
| title | The Effect of High-Pressure Homogenization Conditions on the Physicochemical Properties and Stability of Designed Fluconazole-Loaded Ocular Nanoemulsions |
| title_full | The Effect of High-Pressure Homogenization Conditions on the Physicochemical Properties and Stability of Designed Fluconazole-Loaded Ocular Nanoemulsions |
| title_fullStr | The Effect of High-Pressure Homogenization Conditions on the Physicochemical Properties and Stability of Designed Fluconazole-Loaded Ocular Nanoemulsions |
| title_full_unstemmed | The Effect of High-Pressure Homogenization Conditions on the Physicochemical Properties and Stability of Designed Fluconazole-Loaded Ocular Nanoemulsions |
| title_short | The Effect of High-Pressure Homogenization Conditions on the Physicochemical Properties and Stability of Designed Fluconazole-Loaded Ocular Nanoemulsions |
| title_sort | effect of high pressure homogenization conditions on the physicochemical properties and stability of designed fluconazole loaded ocular nanoemulsions |
| topic | drug delivery surfactants ocular nanoemulsion high-energy methods process parameters formulation optimization |
| url | https://www.mdpi.com/1999-4923/16/1/11 |
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