Development of a sterile, antimycotic, fast dissolving tablet with extended shelf-life for cornea cold storage medium

Introduction: Cold storage is the gold standard corneal preservation method in the US. However, none of the cold storage media currently on the market contains antimycotics.

Purpose: The aim of this study was to develop a sterile, antimycotic, fast dissolving tablet with dose uniformity and extended shelf-life to be added to corneal storage media with the aim of counteracting fungal contaminations during storage at 4°C.

Material and methods: Lyophilised powder of a soluble antimycotic was blended with two excipients in a NOVINOX mixer and compressed with a Ronchi AR90/23 press. The dissolution time and uniformity of content were measured according to USP. Antimycotic content after dissolution in ECS cold storage medium (AL.CHI.MI.A. S.R.L.) was determined by HPLC. Accelerated stability studies were performed according to ICH guidelines. Sterilization by 3 irradiation doses was evaluated. Antimycotic activity was determined by time-kill studies after Candida spp. inoculation of the ECS medium and incubation at 4°C for 1, 4 and 7 days.

Results: After compression, biconvex, 44 mg and 5-mm tablets with uniform dose content were obtained. Average antimycotic content in the medium was 102%.  Dissolution time at room temperature was 2 and 5 minutes in water and cornea storage medium, respectively. According to accelerated stability studies we assume the absence of degradation for 24 and 36 months at 25°C and 4°C, respectively. Among the tested doses, 25kG gamma ray irradiation allowed to fully maintain tablet specifications. Time-kill studies showed 2log₁₀ and 4log₁₀ decrease of Candida spp. in ECS after 24h, and 7 days of incubation at 4°C, respectively.

Conclusions: The new antimycotic tablet showed dose uniformity and stability. In addition, it showed fast dissolution in the ECS medium, and excellent antimycotic properties at 4°C for 7 days.