Marcin Płaczek, Dorota Barbara Świtkowska, Daria Sławińska, Agnieszka Kinga Marek, Małgorzata Sznitowska, Wioletta Kaliszan

Formulation and stability evaluation of disodium edetate eye drops compounded in a hospital pharmacy

2025-01-14

Introduction. Calcific band keratopathy (CBK) is a degenerative corneal disease characterized by the deposition of grayish to whitish opacities consisting of calcium hydroxyapatite on the corneal surface. The goal of treatment is to remove the calcium opacities and restore a smooth ocular surface. The most widely used method for treating CBK is chelation therapy involving edetate disodium (EDTA-Na) ophthalmic drops. This medicine, however, is not commercially available and requires compounding. The composition of EDTA-Na eye formulations can be found in the literature, but the main problem for Polish pharmacists is access to the active substance, which is unavailable either as a registered pharmaceutical raw material or as a sterile parenteral formulation. The solution to this problem is obtaining the injectable form of the drug in a targeted import procedure and reformulating it to eye drops in a pharmacy.

Objective. The present study was designed to investigate the composition and stability of EDTA-Na ophthalmic drops (2%, w/v) prepared from commercially available concentrated injections of EDTA-Na (20%, w/v) licensed and distributed in Italy under the name “Sodio edetato Monico”.

Materials and Methods. A mixture of normal saline and water for injection (1:1 volume ratio) was used to dilute the EDTA-Na concentrate and the resulting solution was sterilized by filtration and stored in four different containers (minims, plastic bottles, plastic syringes and glass vials) at room temperature (25°C/60% RH) or under refrigeration. The physicochemical stability of the solution was tested by measuring osmotic pressure, pH value, and clarity immediately after formulation (t = 0) and after 1, 7, 14, and 28 days of storage.

Results. The formulated eye drops at t = 0 were in the form of a colorless, transparent solution (97.4 ± 0.4% of light transmittance) and were isotonic (295.7 ± 1.2 mosmol/kg) and isohydric (pH 7.0 ± 0.03). The physicochemical properties of the solution did not change significantly throughout the storage period of 28 days. Osmotic pressure of all tested samples was in the range of 292–306 mosmol/kg, pH value between 6.9–7.1 and light transmittance in the range of 95.8–100%, indicating high stability of the compounded formulation in all tested containers and both storage temperatures (at room conditions and under refrigeration).

Conclusion. It can be concluded that 2% EDTA-Na ophthalmic drops prepared using injectable 20% concentrate of EDTA-Na and a mixture of normal saline and water for injection were stable up to the tested time point of 28 days, irrespective of their storage temperature and type of the container.

Keywords: corneal band keratopathy, eye drops, hospital pharmacy, compounding, stability.

© Farm Pol, 2024, 80(8): 547–554