Synergic Effect of Methyl-β-Cyclodextrin and Hydrophilic Polymers on Nepafenac Solubilization: Development of a 0.3% Ophthalmic Solution
Nepafenac is an anti-inflammatory drug used in ophthalmology, marketed as a suspension due to its low aqueous solubility. A solution formulation could provide better bioavailability than suspension and facilitate single unit doses, avoiding the use of preservatives which are required to maintain ste...
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2025-07-01
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| author | Maria Grazia Saita Fabiola Spitaleri Katia Mangano Danilo Aleo Angela Patti |
| author_facet | Maria Grazia Saita Fabiola Spitaleri Katia Mangano Danilo Aleo Angela Patti |
| author_sort | Maria Grazia Saita |
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| description | Nepafenac is an anti-inflammatory drug used in ophthalmology, marketed as a suspension due to its low aqueous solubility. A solution formulation could provide better bioavailability than suspension and facilitate single unit doses, avoiding the use of preservatives which are required to maintain sterility in multidose packaging. In this study, solubilization of nepafenac was achieved in the presence of randomly methylated β-cyclodextrin (RAMEB) and the actual complexation was assessed by NMR and phase-solubility studies. It was also found that the addition of hydrophilic polymers plays an important role in allowing increased solubilization of nepafenac at the same cyclodextrin concentration. Compared to complexes of nepafenac with other cyclodextrins, only 5% RAMEB was sufficient to solubilize 0.3% (<i>w</i>/<i>v</i>) nepafenac, enabling for the first time the development of an ophthalmic solution that proved chemically and physically stable for 12 months at 25 °C. The formulated solutions of nepafenac were tested for cytotoxicity on human corneal epithelial cells (HCE-2) and the results suggest their potential as a valuable and safe alternative to the commercially available 0.3% (<i>w</i>/<i>v</i>) suspension of the drug. |
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| institution | Kabale University |
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| publishDate | 2025-07-01 |
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| series | Molecules |
| spelling | doaj-art-2987f0d6ea7141ff925ebe47c228fced2025-08-20T03:36:27ZengMDPI AGMolecules1420-30492025-07-013015309010.3390/molecules30153090Synergic Effect of Methyl-β-Cyclodextrin and Hydrophilic Polymers on Nepafenac Solubilization: Development of a 0.3% Ophthalmic SolutionMaria Grazia Saita0Fabiola Spitaleri1Katia Mangano2Danilo Aleo3Angela Patti4MEDIVIS, Via Carnazza 34 C, 95030 Catania, ItalyMEDIVIS, Via Carnazza 34 C, 95030 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 89, 95123 Catania, ItalyMEDIVIS, Via Carnazza 34 C, 95030 Catania, ItalyCNR—Institute of Biomolecular Chemistry, Via Paolo Gaifami 18, 95126 Catania, ItalyNepafenac is an anti-inflammatory drug used in ophthalmology, marketed as a suspension due to its low aqueous solubility. A solution formulation could provide better bioavailability than suspension and facilitate single unit doses, avoiding the use of preservatives which are required to maintain sterility in multidose packaging. In this study, solubilization of nepafenac was achieved in the presence of randomly methylated β-cyclodextrin (RAMEB) and the actual complexation was assessed by NMR and phase-solubility studies. It was also found that the addition of hydrophilic polymers plays an important role in allowing increased solubilization of nepafenac at the same cyclodextrin concentration. Compared to complexes of nepafenac with other cyclodextrins, only 5% RAMEB was sufficient to solubilize 0.3% (<i>w</i>/<i>v</i>) nepafenac, enabling for the first time the development of an ophthalmic solution that proved chemically and physically stable for 12 months at 25 °C. The formulated solutions of nepafenac were tested for cytotoxicity on human corneal epithelial cells (HCE-2) and the results suggest their potential as a valuable and safe alternative to the commercially available 0.3% (<i>w</i>/<i>v</i>) suspension of the drug.https://www.mdpi.com/1420-3049/30/15/3090nepafenaccyclodextrin complexhydrophilic polymersophthalmic solution |
| spellingShingle | Maria Grazia Saita Fabiola Spitaleri Katia Mangano Danilo Aleo Angela Patti Synergic Effect of Methyl-β-Cyclodextrin and Hydrophilic Polymers on Nepafenac Solubilization: Development of a 0.3% Ophthalmic Solution Molecules nepafenac cyclodextrin complex hydrophilic polymers ophthalmic solution |
| title | Synergic Effect of Methyl-β-Cyclodextrin and Hydrophilic Polymers on Nepafenac Solubilization: Development of a 0.3% Ophthalmic Solution |
| title_full | Synergic Effect of Methyl-β-Cyclodextrin and Hydrophilic Polymers on Nepafenac Solubilization: Development of a 0.3% Ophthalmic Solution |
| title_fullStr | Synergic Effect of Methyl-β-Cyclodextrin and Hydrophilic Polymers on Nepafenac Solubilization: Development of a 0.3% Ophthalmic Solution |
| title_full_unstemmed | Synergic Effect of Methyl-β-Cyclodextrin and Hydrophilic Polymers on Nepafenac Solubilization: Development of a 0.3% Ophthalmic Solution |
| title_short | Synergic Effect of Methyl-β-Cyclodextrin and Hydrophilic Polymers on Nepafenac Solubilization: Development of a 0.3% Ophthalmic Solution |
| title_sort | synergic effect of methyl β cyclodextrin and hydrophilic polymers on nepafenac solubilization development of a 0 3 ophthalmic solution |
| topic | nepafenac cyclodextrin complex hydrophilic polymers ophthalmic solution |
| url | https://www.mdpi.com/1420-3049/30/15/3090 |
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