Which alternative to ticarcillin eye drops ?

Conventionally, the 6.6 mg/mL ticarcillin eye drops is prescribed in combination with vancomycin and an aminoglycoside to treat severe keratitis. The pharmaceutical specialty called TICARPEN is the raw material used to prepare these eye drops and is in supply disruption without delay. The aim of this study were 1) to find an alternative which could be prepared as an ophthalmic solution, 2) to develop and validate an analytic method which would allow a stability study.

The study was carried out in three stages:

1. To select the drug, a review of the literature was performed and a working group was set-up including infection disease specialists and pharmacists involved in ophthalmology.
2. The suitable concentration and diluting solvent were determined.
3. The development and the validation of an analytic method for the ticarcillin determination were performed

A total of 79 publications was studied, 19 were pre-selected and 5 were selected in view of the action spectra and the ophthalmologic use. Based on the previous results, infectious disease specialists and pharmacists decided to select the piperacillin as the best alternative. The stability data found in the literature and the compatibility with ocular administration (pH = 5 and osmolality = 340 mOsm/kg) lead to select the concentration of 20mg/mL and the 0.9% sodium chloride to prepare the eye drops. An analytic method allowing a stability study was developed: it was a reversed-phase HPLC method adapted from Marselos S.C. et al (J Pharm Biomed Anal 29 (2007) 787-793). The tests of linearity (6 points ranges, r=0,9998), accuracy (average recovery = 100.23% ; CI95% [99.5% ; 100.95%]), repeatability and intermediate precision (coefficients of variation > 5%) were validated.

These results led us to select 20mg/mL piperacillin eye drops as an alternative to ticarcillin eye drop. An analytical method compatible with the current activity and allowing a stability study was validated. A microbiological and physicochemical stability study is ongoing to define the best conditions of conservation and the expiration date of 20 mg/mL piperacillin eye drops.