Physical, chemical and microbiological stability study of 0.1 mg.mL-1 atropine eye drops

Atropine eye drops 0.1 mg.mL-1 is indicated to slow down juvenile myopia progression. According to the literature, this concentration has the best risk/benefit ratio. The solution is stable for 1 month at room temperature. As it is a chronic treatment, a longer shelf life is necessary to improve patients care. This study aimed to demonstrate the physical, chemical and microbiological stability of 0.1 mg.mL-1 atropine eye drops during 6 months.

The preparation consists in the dilution of a 10 mg.mL-1 atropine solution (1% Atropine single doses FAURE, Europhta) diluted in NaCl 0.9 %, followed by a sterilizing filtration and then aseptic filling process of 5 mL in 10 mL low-density polyethylene (LDPE) vial. Whole process is carried out in an overpressure isolator. Three batches of 30 units were produced and kept away from the light at room temperature for 6 months. Visual inspection, pH, osmolality and atropine concentration were controlled at D0, D7, D15 and every month until M6. Atropine concentration was measured using HPLC-UV which had already been proved as indicating stabilizing method, according to ICH methodological guidelines. The sterility was monitored using BacT/Alert® method (Biomérieux) at D0 and each month.

Atropine remained in ±10% of the target value in the three batches. Osmolality (281.3 mOsm.kg-1) as well as pH (5.4) were kept constant. We didn’t note any variation of the solution aspect (no crystal, no coloration). Sterility was maintained.

This study validate the physical, chemical and microbiological stability of 0,1 mg.mL-1 atropine eye drops conserved inside LDPE conditioning away from the light and at room temperature during six months.