Fluconazole nanoparticles prepared by antisolvent precipitation technique: Physicochemical, in vitro, ex vivo and in vivo ocular evaluation

The goal of this research was to prepare and characterize nanonized particles of the antifungal drug, fluconazole (FLZ) using antisolvent precipitation nanonization technique to improve its ocular permeation. The impact of various concentrations of different stabilizers, namely Pluronic F-127 (PL F...

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Main Authors: Amal El Sayeh F. Abou El Ela, Mohamed Abbas Ibrahim, Yara Alqahtani, Aliyah Almomen, Fadilah Sfouq Aleanizy
Format: Article
Language:English
Published: Springer 2021-06-01
Series:Saudi Pharmaceutical Journal
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Online Access:http://www.sciencedirect.com/science/article/pii/S131901642100075X
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author Amal El Sayeh F. Abou El Ela
Mohamed Abbas Ibrahim
Yara Alqahtani
Aliyah Almomen
Fadilah Sfouq Aleanizy
author_facet Amal El Sayeh F. Abou El Ela
Mohamed Abbas Ibrahim
Yara Alqahtani
Aliyah Almomen
Fadilah Sfouq Aleanizy
author_sort Amal El Sayeh F. Abou El Ela
collection DOAJ
description The goal of this research was to prepare and characterize nanonized particles of the antifungal drug, fluconazole (FLZ) using antisolvent precipitation nanonization technique to improve its ocular permeation. The impact of various concentrations of different stabilizers, namely Pluronic F-127 (PL F 127), Kollicoat IR (KL), hydroxypropyl methylcellulose E3 (HPMC), xanthan gum (XG), polyvinyl pyrrolidone K30 (PVP), and sodium lauryl sulfate (SLS) upon the resulting nanoparticles was investigated. Additionally, the ex vivo release of the FLZ nanonized particles from ophthalmic gel bases was studied by using goat cornea, and the ocular pharmacokinetics of appropriate ophthalmic gel base containing optimized drug nanoparticle formula compared to the untreated drug were studied in rabbits. FLZ nanoparticles were successfully prepared with different concentrations of stabilizers. However, the effects of these stabilizers on nanoparticle size and zeta potential values varied according to the concentration and type of stabilizer used. Based on differential scanning calorimetry, the drug was in its amorphous state in the tested nanoparticle formulations. The results of ex vivo ocular diffusion of the FLZ nanoparticle gel formulations revealed an improvement compared to that with the FLZ untreated gel. Nanoparticle formula (F3) prepared by using 5% PL F127 showed small particle size (352 ± 6.1 nm) with zeta potential value of −18.3 mV with highest ex vivo release rate from goat cornea (100% after 6 h). Moreover, the AUC0-8h from ocular application of FLZ from sodium alginate gel containing nanoparticle formula F3 was 1.4-fold higher than that after its administration in the untreated formula. Based on our findings, the ophthalmic gel formulations containing FLZ nanoparticles enhanced drug corneal permeation and improved the ocular pharmacokinetic parameters.
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spelling doaj-art-39457ce5fdca44ce8ac1740df2941cda2025-08-20T03:55:11ZengSpringerSaudi Pharmaceutical Journal1319-01642021-06-0129657658510.1016/j.jsps.2021.04.018Fluconazole nanoparticles prepared by antisolvent precipitation technique: Physicochemical, in vitro, ex vivo and in vivo ocular evaluationAmal El Sayeh F. Abou El Ela0Mohamed Abbas Ibrahim1Yara Alqahtani2Aliyah Almomen3Fadilah Sfouq Aleanizy4Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; Department of Pharmaceutics, College of Pharmacy, Assiut University, 71526 Assiut, Egypt; Corresponding authors at: Department of Pharmaceutics, College of Pharmacy, King Saud University, Saudi Arabia.Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Al-Azhar University, Assiut, Egypt; Corresponding authors at: Department of Pharmaceutics, College of Pharmacy, King Saud University, Saudi Arabia.Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaThe goal of this research was to prepare and characterize nanonized particles of the antifungal drug, fluconazole (FLZ) using antisolvent precipitation nanonization technique to improve its ocular permeation. The impact of various concentrations of different stabilizers, namely Pluronic F-127 (PL F 127), Kollicoat IR (KL), hydroxypropyl methylcellulose E3 (HPMC), xanthan gum (XG), polyvinyl pyrrolidone K30 (PVP), and sodium lauryl sulfate (SLS) upon the resulting nanoparticles was investigated. Additionally, the ex vivo release of the FLZ nanonized particles from ophthalmic gel bases was studied by using goat cornea, and the ocular pharmacokinetics of appropriate ophthalmic gel base containing optimized drug nanoparticle formula compared to the untreated drug were studied in rabbits. FLZ nanoparticles were successfully prepared with different concentrations of stabilizers. However, the effects of these stabilizers on nanoparticle size and zeta potential values varied according to the concentration and type of stabilizer used. Based on differential scanning calorimetry, the drug was in its amorphous state in the tested nanoparticle formulations. The results of ex vivo ocular diffusion of the FLZ nanoparticle gel formulations revealed an improvement compared to that with the FLZ untreated gel. Nanoparticle formula (F3) prepared by using 5% PL F127 showed small particle size (352 ± 6.1 nm) with zeta potential value of −18.3 mV with highest ex vivo release rate from goat cornea (100% after 6 h). Moreover, the AUC0-8h from ocular application of FLZ from sodium alginate gel containing nanoparticle formula F3 was 1.4-fold higher than that after its administration in the untreated formula. Based on our findings, the ophthalmic gel formulations containing FLZ nanoparticles enhanced drug corneal permeation and improved the ocular pharmacokinetic parameters.http://www.sciencedirect.com/science/article/pii/S131901642100075XNanonizationAntisolvent precipitation nanonizationStabilizersFluconazoleOcular delivery
spellingShingle Amal El Sayeh F. Abou El Ela
Mohamed Abbas Ibrahim
Yara Alqahtani
Aliyah Almomen
Fadilah Sfouq Aleanizy
Fluconazole nanoparticles prepared by antisolvent precipitation technique: Physicochemical, in vitro, ex vivo and in vivo ocular evaluation
Saudi Pharmaceutical Journal
Nanonization
Antisolvent precipitation nanonization
Stabilizers
Fluconazole
Ocular delivery
title Fluconazole nanoparticles prepared by antisolvent precipitation technique: Physicochemical, in vitro, ex vivo and in vivo ocular evaluation
title_full Fluconazole nanoparticles prepared by antisolvent precipitation technique: Physicochemical, in vitro, ex vivo and in vivo ocular evaluation
title_fullStr Fluconazole nanoparticles prepared by antisolvent precipitation technique: Physicochemical, in vitro, ex vivo and in vivo ocular evaluation
title_full_unstemmed Fluconazole nanoparticles prepared by antisolvent precipitation technique: Physicochemical, in vitro, ex vivo and in vivo ocular evaluation
title_short Fluconazole nanoparticles prepared by antisolvent precipitation technique: Physicochemical, in vitro, ex vivo and in vivo ocular evaluation
title_sort fluconazole nanoparticles prepared by antisolvent precipitation technique physicochemical in vitro ex vivo and in vivo ocular evaluation
topic Nanonization
Antisolvent precipitation nanonization
Stabilizers
Fluconazole
Ocular delivery
url http://www.sciencedirect.com/science/article/pii/S131901642100075X
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