Cargando…
Do Ophthalmic Solutions of Amphotericin B Solubilised in 2-Hydroxypropyl-γ-Cyclodextrins Possess an Extended Physicochemical Stability?
Fungal keratitis is a sight-threatening disease for which amphotericin B eye drops is one of the front-line treatments. Unfortunately, there are currently no commercial forms available, and there is little data concerning the long-term stability of compounded formulations based on intravenous dosage...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559369/ https://www.ncbi.nlm.nih.gov/pubmed/32825121 http://dx.doi.org/10.3390/pharmaceutics12090786 |
_version_ | 1783594845653172224 |
---|---|
author | Chennell, Philip Yessaad, Mouloud Abd El Kader, Florence Jouannet, Mireille Wasiak, Mathieu Bouattour, Yassine Sautou, Valérie |
author_facet | Chennell, Philip Yessaad, Mouloud Abd El Kader, Florence Jouannet, Mireille Wasiak, Mathieu Bouattour, Yassine Sautou, Valérie |
author_sort | Chennell, Philip |
collection | PubMed |
description | Fungal keratitis is a sight-threatening disease for which amphotericin B eye drops is one of the front-line treatments. Unfortunately, there are currently no commercial forms available, and there is little data concerning the long-term stability of compounded formulations based on intravenous dosages forms. New formulations of amphotericin B ophthalmic solutions solubilised with γ-cyclodextrins have shown promising in-vitro results, but stability data is also lacking. The objective of this study was therefore to investigate the stability of a formulation of ready-to-use amphotericin B solubilised in 2-hydroxypropyl-γ-cyclodextrins (AB-HP-γ-CD), for 350 days. An amphotericin B deoxycholate (ABDC) formulation was used as a comparator. Analyses used were the following: visual inspection, turbidity, osmolality and pH measurements, amphotericin B quantification by a stability-indicating liquid chromatography method, breakdown product research, and sterility assay. AB-HP-γ-CD formulation showed signs of chemical instability (loss of amphotericin B) after 28 and 56 days at 25 °C and 5 °C. Adding an antioxidant (ascorbic acid) to the formulation did not improve stability. ABDC formulation showed signs of physical instability (increased turbidy and amphotericin B precipitation) after 28 days and 168 days at 25 °C and 5 °C. As such, AB-HP-γ-CD formulation does not provide long-term stability for ophthalmic amphotericin B solutions. |
format | Online Article Text |
id | pubmed-7559369 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75593692020-10-26 Do Ophthalmic Solutions of Amphotericin B Solubilised in 2-Hydroxypropyl-γ-Cyclodextrins Possess an Extended Physicochemical Stability? Chennell, Philip Yessaad, Mouloud Abd El Kader, Florence Jouannet, Mireille Wasiak, Mathieu Bouattour, Yassine Sautou, Valérie Pharmaceutics Article Fungal keratitis is a sight-threatening disease for which amphotericin B eye drops is one of the front-line treatments. Unfortunately, there are currently no commercial forms available, and there is little data concerning the long-term stability of compounded formulations based on intravenous dosages forms. New formulations of amphotericin B ophthalmic solutions solubilised with γ-cyclodextrins have shown promising in-vitro results, but stability data is also lacking. The objective of this study was therefore to investigate the stability of a formulation of ready-to-use amphotericin B solubilised in 2-hydroxypropyl-γ-cyclodextrins (AB-HP-γ-CD), for 350 days. An amphotericin B deoxycholate (ABDC) formulation was used as a comparator. Analyses used were the following: visual inspection, turbidity, osmolality and pH measurements, amphotericin B quantification by a stability-indicating liquid chromatography method, breakdown product research, and sterility assay. AB-HP-γ-CD formulation showed signs of chemical instability (loss of amphotericin B) after 28 and 56 days at 25 °C and 5 °C. Adding an antioxidant (ascorbic acid) to the formulation did not improve stability. ABDC formulation showed signs of physical instability (increased turbidy and amphotericin B precipitation) after 28 days and 168 days at 25 °C and 5 °C. As such, AB-HP-γ-CD formulation does not provide long-term stability for ophthalmic amphotericin B solutions. MDPI 2020-08-19 /pmc/articles/PMC7559369/ /pubmed/32825121 http://dx.doi.org/10.3390/pharmaceutics12090786 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chennell, Philip Yessaad, Mouloud Abd El Kader, Florence Jouannet, Mireille Wasiak, Mathieu Bouattour, Yassine Sautou, Valérie Do Ophthalmic Solutions of Amphotericin B Solubilised in 2-Hydroxypropyl-γ-Cyclodextrins Possess an Extended Physicochemical Stability? |
title | Do Ophthalmic Solutions of Amphotericin B Solubilised in 2-Hydroxypropyl-γ-Cyclodextrins Possess an Extended Physicochemical Stability? |
title_full | Do Ophthalmic Solutions of Amphotericin B Solubilised in 2-Hydroxypropyl-γ-Cyclodextrins Possess an Extended Physicochemical Stability? |
title_fullStr | Do Ophthalmic Solutions of Amphotericin B Solubilised in 2-Hydroxypropyl-γ-Cyclodextrins Possess an Extended Physicochemical Stability? |
title_full_unstemmed | Do Ophthalmic Solutions of Amphotericin B Solubilised in 2-Hydroxypropyl-γ-Cyclodextrins Possess an Extended Physicochemical Stability? |
title_short | Do Ophthalmic Solutions of Amphotericin B Solubilised in 2-Hydroxypropyl-γ-Cyclodextrins Possess an Extended Physicochemical Stability? |
title_sort | do ophthalmic solutions of amphotericin b solubilised in 2-hydroxypropyl-γ-cyclodextrins possess an extended physicochemical stability? |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559369/ https://www.ncbi.nlm.nih.gov/pubmed/32825121 http://dx.doi.org/10.3390/pharmaceutics12090786 |
work_keys_str_mv | AT chennellphilip doophthalmicsolutionsofamphotericinbsolubilisedin2hydroxypropylgcyclodextrinspossessanextendedphysicochemicalstability AT yessaadmouloud doophthalmicsolutionsofamphotericinbsolubilisedin2hydroxypropylgcyclodextrinspossessanextendedphysicochemicalstability AT abdelkaderflorence doophthalmicsolutionsofamphotericinbsolubilisedin2hydroxypropylgcyclodextrinspossessanextendedphysicochemicalstability AT jouannetmireille doophthalmicsolutionsofamphotericinbsolubilisedin2hydroxypropylgcyclodextrinspossessanextendedphysicochemicalstability AT wasiakmathieu doophthalmicsolutionsofamphotericinbsolubilisedin2hydroxypropylgcyclodextrinspossessanextendedphysicochemicalstability AT bouattouryassine doophthalmicsolutionsofamphotericinbsolubilisedin2hydroxypropylgcyclodextrinspossessanextendedphysicochemicalstability AT sautouvalerie doophthalmicsolutionsofamphotericinbsolubilisedin2hydroxypropylgcyclodextrinspossessanextendedphysicochemicalstability |