Stability of an ophthalmic micellar formulation of cyclosporine A in unopened multidose eyedroppers and in simulated use conditions

Chennell, Philip; Delaborde, L.; Wasiak, Mathieu; Jouannet, Mireille; Feschet-Chassot, E.; Chiambaretta, Frédéric; Sautou, V.

doi:10.1016/j.ejps.2017.01.024

Cited by 16 publications

(11 citation statements)

References 15 publications

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“…These results were in good accordance with those reported by Chennel et al [22], that evaluated the stability of cyclosporine A in an eye drop formulation even if limited at 30 days under usage conditions, observing no significant degradative effect. However, in this last study the evaluation of active substances behavior was not extended to prolonged storage period and to simulated usage conditions as done in the present study, that is important since the frequent instillations required by the therapy regimen, often involve the bottle opening and closing more than 3 time per day that can lead to cyclosporine A and tacrolimus degradation trend more consistent especially after 30 days.…”

Section: Stability Of Tacrolimus and Cyclosporine A In Eye Drop Formusupporting

confidence: 93%

“…LDPE containers were used to store all involved formulations in the present research. The container quality represents a crucial point since the purity of a medicinal preparation may also change during storage due to leaching of chemical or chemicals into the drug preparation from the container materials, from the labels on the containers, or from the environment where the packaged ophthalmic product is stored [22]. Thus, containers used for packaging medicinal preparations can significantly affect the stability and purity of the preparations as well.…”

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confidence: 99%

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Stability and Safety Traits of Novel Cyclosporine A and Tacrolimus Ophthalmic Galenic Formulations Involved in Vernal Keratoconjunctivitis Treatment by a High-Resolution Mass Spectrometry Approach

et al. 2020

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In this study, a sensitive quantitative method based on high performance liquid chromatography combined with high-resolution mass spectrometry, Q ExactiveTM-Orbitrap® was set up and applied for the determination of the immunosuppressor agents cyclosporine A and tacrolimus in novel ethanol-free ophthalmic formulations for the treatment of Vernal keratoconjunctivitis. Different storage parameters in terms of storage temperatures and practical usage conditions were investigated to assess the stability of all formulations during shelf life simulating the real conditions as well to confirm the feasibility of use of ethanol-free products. The methodology was linear (r2 = 0.995) over the concentration range 0–200 ng/mL, and its selectivity, precision, accuracy and recovery were all within the required limits. Under different conditions (storage period 0–90 days, 5–25 °C, unopened/usage simulated conditions), our results revealed that both active pharmaceutical ingredients (API) show satisfactory stability up to 30 days of storage/usage, with a significant and consistent concentration decline of cyclosporine A after this time point when its hydroalcoholic formulation was kept at 25 °C.

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Section: Stability Of Tacrolimus and Cyclosporine A In Eye Drop Formusupporting

confidence: 93%

mentioning

confidence: 99%

Stability and Safety Traits of Novel Cyclosporine A and Tacrolimus Ophthalmic Galenic Formulations Involved in Vernal Keratoconjunctivitis Treatment by a High-Resolution Mass Spectrometry Approach

et al. 2020

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“…The 10 mg.ml −1 concentration drops and 20 mg.ml −1 concentration drops didn't exhibit any significant variation between the different eyedroppers. Those concentrations also stayed in the 90-110 % range all along the study, a sole lower limit of confidence interval on the third analytical time for 20 mg.ml −1 LDPE-Si eyedroppers was found at 18.2 mg.ml −1 (86.0 % of RC), which is consistent with a previously published study (7). The concentration is here 10 to 20 folds the previous one, so we can highly suspect a saturation phenomenon of adsorption sites, consuming few enough of the molecules so it doesn't reflect on the drops' concentration.…”

Section: Discussionsupporting

confidence: 81%

“…Cyclosporine micellar solutions were prepared according to the method described by Chennell et al (7). For those and for all solutions to be tested in a different eyedropper from the commercial one, reconditioning into the tested eyedroppers was realized under the laminar air flow of an ISO 4.8 microbiological safety cabinet to prevent microbial contamination.…”

Section: Reconditioning and Storagementioning

confidence: 99%

A Sorption Study between Ophthalmic Drugs and Multi Dose Eyedroppers in Simulated Use Conditions

Basle

Chennell

Sautou

2017

Pharmaceutical Technology in Hospital Pharmacy

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AbstractPreservative free ophthalmic formulations need to be packaged either as single doses, or using specially designed sterility preserving multidose eyedroppers. Our objective was to evaluate potential sorption phenomena between a device with a silicone sterility preserving membrane and the delivered drops of several ophthalmic solutions. Cyclosporine, rifamycin, latanoprost, timolol and norfloxacin were used as model drugs. Quantification of the active substance in delivered drops (1 to 4 drops per day) from low density polyethylene (LDPE) bottles without any sterility preserving device and from LDPE bottles with a sterility preserving silicone membrane (LDPE-Si) was performed for 14 days (n≥3), using validated HPLC methods. For cyclosporine, mean concentrations did not vary by more than 10 % from reference concentrations for either LDPE or LDPE-Si eyedroppers, but for LDPE-Si, the concentrations of the 1 mg.ml-1 cyclosporine micellar solution were found to be significantly lower than for those from LDPE eyedroppers (p=0.0127). For LDPE-Si, rifamycin mean concentrations decreased by 11.2 % throughout the 14 day study period, but didn’t vary by more than 10 % for LDPE and glass eyedroppers. However, rifamycin concentrations from LDPE-Si were not significantly different from those from LDPE eyedroppers. For latanoprost, whilst mean concentrations did not vary by more than 10 % from reference concentration for LDPE eyedroppers, for LDPE-Si eyedroppers concentrations decreased by 76.4 % at their lowest concentration and never returned to their initial level. For timolol and norfloxacin, mean concentrations did not vary by more than 10 % for either LDPE or LDPE-Si eyedroppers and no significant difference was found between the 2 eyedroppers concentrations. Our results are in favor of an absence of significant sorption between LDPE-Si eyedroppers for timolol or norfloxacin ophthalmic solutions. Further studies should be performed on cyclosporine ophthalmic micellar solutions and rifamycin ophthalmic solutions before any definite conclusions can be made. Finally, our results show that latanoprost ophthalmic solutions shouldn’t be used with LDPE-Si eyedroppers as the loss of active substance would cause a sever under-dosing.

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“…Indeed, few studies have been published concerning atropine eyedrops stability, but the analyses were either lacking several tests or suffered from shortcomings concerning breakdown product research [ 24 , 25 , 26 ]. As single-dose container technology is not readily available to compounding pharmacies, multidose eyedroppers (often in low dose polypropylene) are the most used container and therefore the most studied [ 27 , 28 , 29 , 30 ]. However, not all of those devices possess a system allowing their content to be preservative-free, and their contents must therefore be preserved.…”

Section: Introductionmentioning

confidence: 99%

Stability of Ophthalmic Atropine Solutions for Child Myopia Control

et al. 2020

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Myopia is an ophthalmic condition affecting more than 1/5th of the world population, especially children. Low-dose atropine eyedrops have been shown to limit myopia evolution during treatment. However, there are currently no commercial industrial forms available and there is little data published concerning the stability of medications prepared by compounding pharmacies. The objective of this study was to evaluate the stability of two 0.1 mg/mL atropine formulations (with and without antimicrobiobial preservatives) for 6 months in two different low-density polyethylene (LDPE) multidose eyedroppers. Analyses used were the following: visual inspection, turbidity, chromaticity measurements, osmolality and pH measurements, atropine quantification by a stability-indicating liquid chromatography method, breakdown product research, and sterility assay. In an in-use study, atropine quantification was also performed on the drops emitted from the multidose eyedroppers. All tested parameters remained stable during the 6 months period, with atropine concentrations above 94.7% of initial concentration. A breakdown product (tropic acid) did increase slowly over time but remained well below usually admitted concentrations. Atropine concentrations remained stable during the in-use study. Both formulations of 0.1 mg/mL of atropine (with and without antimicrobial preservative) were proved to be physicochemically stable for 6 months at 25 °C when stored in LDPE bottles, with an identical microbial shelf-life.

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Stability of an ophthalmic micellar formulation of cyclosporine A in unopened multidose eyedroppers and in simulated use conditions

Cited by 16 publications

References 15 publications

Stability and Safety Traits of Novel Cyclosporine A and Tacrolimus Ophthalmic Galenic Formulations Involved in Vernal Keratoconjunctivitis Treatment by a High-Resolution Mass Spectrometry Approach

Stability and Safety Traits of Novel Cyclosporine A and Tacrolimus Ophthalmic Galenic Formulations Involved in Vernal Keratoconjunctivitis Treatment by a High-Resolution Mass Spectrometry Approach

A Sorption Study between Ophthalmic Drugs and Multi Dose Eyedroppers in Simulated Use Conditions

Stability of Ophthalmic Atropine Solutions for Child Myopia Control

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