A stability study of 25 mg/mL phenylephrine hydrochloride and 5 mg/mL tropicamide eye drops

Prematurity’s retinopathy is detected by a regular fundus performed during the first weeks of life, using a mydriatric solution. In 2012 the French National Agency for Medicines and Health product Safety expressed a recommendation about the preferential use of phenylephrine 2.5% or 1 % and tropicamide rather than atropine. Thus, we decided with the ophthalmologic referent of the neonatology unit to develop an eye drops combining 25 mg/mL (2.5%) phenylephrine hydrochloride and 5 mg/mL (0.5%) tropicamide. This preparation leads to a satisfactorily mydriasis in thirty minutes after two instillations spaced by 15 minutes.

The aim of this study was to demonstrate the physical, chemical and microbiological stability of this eye drops.

The preparation is carried out inside an overpressure isolator placed in a grade D environment. The process consists in dissolving the phenylephrine powder (INRESA) into the tropicamide solution (Mydriaticum® unidoses 0.5 %, THÉA), followed by a sterilizing filtration and then aseptic filling process of 1 mL in high-density polyethylene bottle vials. Three manipulators produced a batch of 40 units each. Vials were kept away from the light at room temperature for 3 months. The content of active substances was measured using HPLC-UV, which had already been proved as indicating stabilizing method. We also performed a control of pH and osmolality, and inspected visually the solution aspect. The bacteriological sterility was monitored using BacT/Alert® (BIOMERIEUX) application.[...]

Both active compound contents remained in ±5% of the target value in the three batches. We didn’t note any variation of the solution aspect. pH (4.99±0.02) as well as osmolarity (512.6±4.7) were kept constant. Sterility was maintained. This study allowed to validate the physical, chemical and microbiological stability of phenylephrine hydrochloride and tropicamide eye drops conserved inside LDPE conditioning, away from the light and at room temperature during three months.