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

Abstract

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.

Hospital-prepared low-dose atropine eye drops for myopia progression control using atropine sulfate injection diluted in normal saline and lubricants

“…Our experiment concurs with previous studies on in-house antifungal [8] and immunosuppressive [7] eyedrop preparations. We also demonstrate similar e cacy of atropine sulfate in various solvents.…”

“…Several commercial 0.01% atropine eye drops have been approved by the Food and Drug Administration for myopia progression control only in some countries. Hence, in-house preparation by diluting a commercial atropine sulfate eye-drop with sterile water [5][6][7][8] or balanced salt solution (normal saline) has been applied [9,10]. A practical technique is drawing 0.1ml of 1% atropine sulfate eye-drop and injecting it into a 10ml bottle of either commercial arti cial tear or balanced salt solution eye-drops.…”

“…Alternatively, we anticipated that the atropine sulfate injection commonly used for emergency treatment of bradycardia could also be used for the in-house preparation of the diluted atropine eye-drop for myopia progression control. Similar approach has been accomplished for antifungal (Voriconazole) [8] and immunosuppressive (Cyclosporine A and Tacrolimus) [7] sterile-water-based eye-drops. Atropine sulfate injection is readily available in any healthcare facility whereas the injection formulation usually contains no preservatives which are always of concern in the eye-drop formulation [10].…”

Stability of Ophthalmic Atropine Solutions for Child Myopia Control

“…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.…”

Do Ophthalmic Solutions of Amphotericin B Solubilised in 2-Hydroxypropyl-γ-Cyclodextrins Possess an Extended Physicochemical Stability?

“…Eliminating oxygen could also help reduce decay [ 48 ], but, although achievable, such a step could complexify the preparation steps, as the apparatus needed is not readily available to all compounding pharmacies. Another solution might be to try alternative excipients, such as polyethoxylated castor oil and polyvinylpyrrolidone, as they have shown to be able to solubilize other lipophilic compounds like cyclosporine A and tacrolimus [ 54 , 55 ]. Otherwise, and for resource-rich countries, the use of high-cost liposomal formulations could provide an acceptable, yet expensive, alternative, albeit without providing a long-term stability solution for ready-to use eye drops of amphotericin B.…”