Physicochemical Stability of a Novel Tacrolimus Ophthalmic Formulation for the Treatment of Ophthalmic Inflammatory Diseases
Tacrolimus is an immunosuppressant used to treat a large variety of inflammatory or immunity-mediated ophthalmic diseases. However, there are currently no commercial industrial forms available that can provide relief to patients. Various ophthalmic formulations have been reported in the literature,...
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| Format: | Article |
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MDPI AG
2022-01-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/1/118 |
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| author | Marion Barrieu Philip Chennell Mouloud Yessaad Yassine Bouattour Mathieu Wasiak Mireille Jouannet Yoann Le Basle Valérie Sautou |
| author_facet | Marion Barrieu Philip Chennell Mouloud Yessaad Yassine Bouattour Mathieu Wasiak Mireille Jouannet Yoann Le Basle Valérie Sautou |
| author_sort | Marion Barrieu |
| collection | DOAJ |
| description | Tacrolimus is an immunosuppressant used to treat a large variety of inflammatory or immunity-mediated ophthalmic diseases. However, there are currently no commercial industrial forms available that can provide relief to patients. Various ophthalmic formulations have been reported in the literature, but their stability has only been tested over short periods. The objective of this study was to evaluate the physicochemical stability of a preservative-free tacrolimus formulation (0.2 and 1 mg/mL) at three storage temperatures (5 °C, 25 °C and 35 °C) for up to nine months in a multidose eyedropper. Analyses performed were the following: visual inspection and chromaticity, turbidity, viscosity, size of micelles, osmolality and pH measurements, tacrolimus quantification by a stability-indicating liquid chromatography method, breakdown product research, and sterility assay. In an in-use study, tacrolimus quantification was also performed on the drops emitted from the eyedroppers. All tested parameters remained stable during the nine month period when the eyedrops were stored at 5 °C. However, during storage at 25 °C and 35 °C, several signs of chemical instability were detected. Furthermore, a leachable compound originating from a silicone part of the eyedropper was detected during the in-use assay. Overall, the 0.2 mg/mL and 1 mg/mL tacrolimus ophthalmic solutions were physicochemically stable for up to nine months when stored at 5 °C. |
| first_indexed | 2024-03-10T00:42:49Z |
| format | Article |
| id | doaj.art-10e15dd51dfb4241b882e6410de2dac7 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T00:42:49Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-10e15dd51dfb4241b882e6410de2dac72023-11-23T15:04:11ZengMDPI AGPharmaceutics1999-49232022-01-0114111810.3390/pharmaceutics14010118Physicochemical Stability of a Novel Tacrolimus Ophthalmic Formulation for the Treatment of Ophthalmic Inflammatory DiseasesMarion Barrieu0Philip Chennell1Mouloud Yessaad2Yassine Bouattour3Mathieu Wasiak4Mireille Jouannet5Yoann Le Basle6Valérie Sautou7CHU Clermont-Ferrand, Pôle Pharmacie, F-63003 Clermont-Ferrand, FranceUniversité Clermont Auvergne, CHU Clermont Ferrand, Clermont Auvergne INP, CNRS, ICCF, F-63000 Clermont-Ferrand, FranceCHU Clermont-Ferrand, Pôle Pharmacie, F-63003 Clermont-Ferrand, FranceUniversité Clermont Auvergne, CHU Clermont Ferrand, Clermont Auvergne INP, CNRS, ICCF, F-63000 Clermont-Ferrand, FranceCHU Clermont-Ferrand, Pôle Pharmacie, F-63003 Clermont-Ferrand, FranceCHU Clermont-Ferrand, Pôle Pharmacie, F-63003 Clermont-Ferrand, FranceUniversité Clermont Auvergne, CHU Clermont Ferrand, Clermont Auvergne INP, CNRS, ICCF, F-63000 Clermont-Ferrand, FranceUniversité Clermont Auvergne, CHU Clermont Ferrand, Clermont Auvergne INP, CNRS, ICCF, F-63000 Clermont-Ferrand, FranceTacrolimus is an immunosuppressant used to treat a large variety of inflammatory or immunity-mediated ophthalmic diseases. However, there are currently no commercial industrial forms available that can provide relief to patients. Various ophthalmic formulations have been reported in the literature, but their stability has only been tested over short periods. The objective of this study was to evaluate the physicochemical stability of a preservative-free tacrolimus formulation (0.2 and 1 mg/mL) at three storage temperatures (5 °C, 25 °C and 35 °C) for up to nine months in a multidose eyedropper. Analyses performed were the following: visual inspection and chromaticity, turbidity, viscosity, size of micelles, osmolality and pH measurements, tacrolimus quantification by a stability-indicating liquid chromatography method, breakdown product research, and sterility assay. In an in-use study, tacrolimus quantification was also performed on the drops emitted from the eyedroppers. All tested parameters remained stable during the nine month period when the eyedrops were stored at 5 °C. However, during storage at 25 °C and 35 °C, several signs of chemical instability were detected. Furthermore, a leachable compound originating from a silicone part of the eyedropper was detected during the in-use assay. Overall, the 0.2 mg/mL and 1 mg/mL tacrolimus ophthalmic solutions were physicochemically stable for up to nine months when stored at 5 °C.https://www.mdpi.com/1999-4923/14/1/118tacrolimusophthalmic solutionphysicochemical stabilitycontainer-content interactionleachable compound |
| spellingShingle | Marion Barrieu Philip Chennell Mouloud Yessaad Yassine Bouattour Mathieu Wasiak Mireille Jouannet Yoann Le Basle Valérie Sautou Physicochemical Stability of a Novel Tacrolimus Ophthalmic Formulation for the Treatment of Ophthalmic Inflammatory Diseases Pharmaceutics tacrolimus ophthalmic solution physicochemical stability container-content interaction leachable compound |
| title | Physicochemical Stability of a Novel Tacrolimus Ophthalmic Formulation for the Treatment of Ophthalmic Inflammatory Diseases |
| title_full | Physicochemical Stability of a Novel Tacrolimus Ophthalmic Formulation for the Treatment of Ophthalmic Inflammatory Diseases |
| title_fullStr | Physicochemical Stability of a Novel Tacrolimus Ophthalmic Formulation for the Treatment of Ophthalmic Inflammatory Diseases |
| title_full_unstemmed | Physicochemical Stability of a Novel Tacrolimus Ophthalmic Formulation for the Treatment of Ophthalmic Inflammatory Diseases |
| title_short | Physicochemical Stability of a Novel Tacrolimus Ophthalmic Formulation for the Treatment of Ophthalmic Inflammatory Diseases |
| title_sort | physicochemical stability of a novel tacrolimus ophthalmic formulation for the treatment of ophthalmic inflammatory diseases |
| topic | tacrolimus ophthalmic solution physicochemical stability container-content interaction leachable compound |
| url | https://www.mdpi.com/1999-4923/14/1/118 |
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