Stability of Cyclosporine 1% in Artificial Tears

Abstract

We wished to determine the stability of frozen, refrigerated, and room temperature topical cyclosporine 1% in artificial tears (Tears Plus). Cyclosporine 1% eye drops were made in artificial tears prior to the manufacturers recommendations of using a lipid soluble vehicle, such as olive oil. Patients preferred the artificial tears preparation over the oil based cyclosporine product. Because of the good clinical response and the reluctance of patients to change to the oil vehicle product, we determined the stability of cyclosporine 1% in artificial tears. Cyclosporine 1% was prepared in artificial tears (polyvinyl alcohol 1.4% and povidone 0.6%) by adding 1 ml of the injectable (50 mg/ml) cyclosporine into 4 ml of the artificial tears solution. Each bottle was frozen at -20 degrees C for one month and then the cyclosporine concentration was determined after thawing and refrigeration or storage at room temperature. Refrigerated stability was determined after thawing for up to 28 days and room temperature stability was determined for up to 1 week after thawing. Cyclosporine concentration was determined by HPLC analysis. None of the samples exhibited any significant loss of cyclosporine at any time period. Frozen cyclosporine appears stable when frozen in a 1% solution for one month. Cyclosporine 1% in artificial tears is stable for up to 28 days in the refrigerator or at least 7 days at room temperature. Because of the ease of preparation, the proven clinical effectiveness of the product and better patient acceptance, we continue to make this product.

Does the temperature of an artificial tear affect its comfort?

“…Previous studies have evaluated the effect of refrigerating eye‐drops and its implication on various parameters such as drop stability and their ability to relieve symptoms upon instillation. A study by Fujishima et al revealed that participants were more comfortable with refrigerated artificial tears (preservative free Soft Santear, Santen Pharmaceutical Co., Osaka, Japan) at 4°C than room temperature or warmed to 36°C.…”

Topical Cyclosporin A in the treatment of acute graft rejection: a randomized controlled trial

“…data, 2001). In this previous open study we had made 1% drops by adding 2 mL Cyclosporin injection 50 mg in 1 mL (Sandimmum, Novartis, Basel, Switzerland) to 8 mL of Tears Plus (Allergan, Irvine, CA, USA) 12 …”

“…In this previous open study we had made 1% drops by adding 2 mL Cyclosporin injection 50 mg in 1 mL (Sandimmum, Novartis, Basel, Switzerland) to 8 mL of Tears Plus (Allergan, Irvine, CA, USA). 12 Recently, Restasis (CsA 0.05%) has been made commercially available after Food and Drug Administration (USA) approval for treatment of dry eyes. This novel emulsion of CsA has been shown to have a good safety profile with no systemic side-effects.…”

A water-soluble prodrug of cyclosporine A for ocular application: A stability study

“…CsA is itself very stable due to its lipophilic nature and its cyclic structure (Kumar et al, 2001). It was shown to be stable over 7 days at room temperature and up to 28 days at 4 • C when formulated at 1% in artificial tears (Fiscella et al, 1996). Although UNIL088 has a longer shelf-life at pH 5 than at pH 6 and 7, a neutral pH must be preferred for the formulation because of its biocompatibility.…”