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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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Autores principales: Barrieu, Marion, Chennell, Philip, Yessaad, Mouloud, Bouattour, Yassine, Wasiak, Mathieu, Jouannet, Mireille, Le Basle, Yoann, Sautou, Valérie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778879/
https://www.ncbi.nlm.nih.gov/pubmed/35057013
http://dx.doi.org/10.3390/pharmaceutics14010118
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author Barrieu, Marion
Chennell, Philip
Yessaad, Mouloud
Bouattour, Yassine
Wasiak, Mathieu
Jouannet, Mireille
Le Basle, Yoann
Sautou, Valérie
author_facet Barrieu, Marion
Chennell, Philip
Yessaad, Mouloud
Bouattour, Yassine
Wasiak, Mathieu
Jouannet, Mireille
Le Basle, Yoann
Sautou, Valérie
author_sort Barrieu, Marion
collection PubMed
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.
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spelling pubmed-87788792022-01-22 Physicochemical Stability of a Novel Tacrolimus Ophthalmic Formulation for the Treatment of Ophthalmic Inflammatory Diseases Barrieu, Marion Chennell, Philip Yessaad, Mouloud Bouattour, Yassine Wasiak, Mathieu Jouannet, Mireille Le Basle, Yoann Sautou, Valérie Pharmaceutics Article 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. MDPI 2022-01-04 /pmc/articles/PMC8778879/ /pubmed/35057013 http://dx.doi.org/10.3390/pharmaceutics14010118 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Barrieu, Marion
Chennell, Philip
Yessaad, Mouloud
Bouattour, Yassine
Wasiak, Mathieu
Jouannet, Mireille
Le Basle, Yoann
Sautou, Valérie
Physicochemical Stability of a Novel Tacrolimus Ophthalmic Formulation for the Treatment of Ophthalmic Inflammatory Diseases
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778879/
https://www.ncbi.nlm.nih.gov/pubmed/35057013
http://dx.doi.org/10.3390/pharmaceutics14010118
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