Preparation and Stability of Voriconazole Eye Drop Solution

Abstract

The combined systemic and topical administration of voriconazole has successfully been used to treat keratomycosis. Because no voriconazole eye drop product is commercially available, we prepared a sterile eye drop solution (10 mg/ml). Voriconazole remains stable over 30 days, providing an eye drop solution suitable for use for the topical treatment of fungal keratitis.Voriconazole is a recent triazole antifungal agent that is highly effective against Aspergillus, Fusarium, and Candida species. Furthermore, voriconazole is one of the few drugs active against Scedosporium apiospermum (10). These fungi may cause severe keratomycosis, a rare but sight-threatening infection of the cornea (4).The conventional management of keratomycosis includes the local application, with or without systemic administration, of antifungal drugs. The use of voriconazole for the treatment of visually devastating disease due to Scedosporium apiospermum has been proposed (7,14). The treatment combines the systemic and the topical administration of voriconazole (6). More recently, voriconazole has successfully been used for the treatment of keratitis caused by a variety of fungi, most commonly, Aspergillus species, Fusarium species, and Candida species (2, 8, 9, 11).As is the case for many antimicrobial agents, no voriconazole eye drop solution is commercially available. Although several authors have reported on the potential of voriconazole for use for topical ophthalmic administration, none of them focused on the stability or the storage of voriconazole. This paper describes how we prepared a voriconazole ophthalmic solution. In addition, we performed a study in order to assess the stability of this solution over 1 month. Finally, the sterility of the preparation was evaluated.On the basis of information available in the literature (8, 9, 11), a 1% (10-mg/ml) voriconazole eye drop solution was prepared by using the branded product: voriconazole powder for solution for intravenous infusion (Vfend; Pfizer). Voriconazole powder (200 mg) was reconstituted with 19 ml of water for injections in order to obtain 20 ml of a 10-mg/ml voriconazole solution. Sterile filtration through a 0.20-m-pore-size filter was then performed. Finally, the voriconazole solution was packaged in a specific sterile vial for use as an eye drop solution. In order to keep the solution sterile, reconstitution was performed according to recommendations for aseptic preparation.In order to cure keratomycosis, antifungal eye drops must be administered over a long period (at least 6 weeks). Although the eye drop solution needs to be kept for several days after preparation for its use by a patient, its stability was unknown. Therefore, in order to assess the stability of the voriconazole eye drop solution, three batches of the formulation were stored for up to 30 days under different projected conditions suitable for its routine use. Under condition A, the solutions (n ϭ 6) were kept at room temperature (24 Ϯ 3°C) and were not protected from light (colorless type I glass via...

Eye

“…amphotericin B, fluconazole, mitomycin, and voriconazole [123][124][125][126]. A sterile product with the active substance (i.e.…”

Antifúngicos em infecções oculares: drogas e vias de administração

“…Administered at a concentration of 1 mg/ml, it was effective in the treatment of keratitis by Candida, Aspergillus, Fusarium, Scedosporium, and Paecilomyces, among others (97)(98)(99)(100)(101) . Its advantages compared to polyenes include its greater stability to light and temperature, remaining effective for up to 30 days (102,103) . Studies in horses showed drug penetration even with epithelial integrity (104) .…”

Topical Voriconazole Drops With and Without Intrastromal Voriconazole Injection for Treatment of Deep or Resistant Fungal Keratitis

“…Voriconazole is stable under regular storage temperatures (+4°C and room temperature), and exposure to light does not cause its degradation [5]. Voriconazole, intrastromal injection and/or eye drops , was started as soon as the diagnosis was confirmed both clinically and by smears and/or cultures, along with topical antibiotic eye drops (moxifloxacin hydrochloride 0.5%) to treat any associated bacterial infection and topical mydriatic cycloplegic eye drops (atropine sulphate 1%) along with systemic non-steroidal anti-inflammatory drugs.…”