Could we package atropine eye drops 0.1 mg.mL-1 and 0.5 mg.mL-1 in Novelia® bottles ?
Our production unit aims to replace the current packaging of 0.1 mg.mL-1 and 0.5 mg.mL-1 atropine eye drops (Standard multidose bottles in Low Density Polyethylene-LDPE) with Novelia® bottles (Nemera). Novelia® is a multidose system in LDPE fitted with a tip including a silicone valve. This valve allows to preserve solution sterility for up to 30 days after opening. The objective is to determine whether Novelia® bottles are suitable for packaging atropine eye drops by assessing container-content interactions and validating sterility 30 days after opening in simulated use conditions.
A batch of each eye drops concentration is prepared. The eye drops are obtained by diluting a 10 mg/mL atropine solution (Atropine single doses 1% FAURE, Europhta) in 0.9% NaCl followed by sterilizing filtration and aseptic filling process in LDPE bottles (n=5/batch) and in Novelia® bottles (n=5/batch). The potential interactions between Novelia® system and atropine solution are assessed by comparing the evolution of atropine concentration in drops extracted from Novelia® bottles with that of LDPE bottles (according to the methodology of Yoan Le Basle & al. PTHP 2017). This monitoring is carried out for 30 days by a previously validated HPLC method.
A reference concentration (RC) of each batch is measured on a sample of the batch on the day of production. Then, for each vial, 2 drops (40µL) are extracted per day (1 drop = 20μL), simulating current use of the eye drops (1 drop per day and per eye). The drops extracted are measured at D1, D2, D3, D4, D8, D15, D22 and D30. They are eliminated the other days. An assay of the residual solution in bottles on D30 is also carried out. In addition, a sterility test by BactAlert® is performed on the residual solution of Novelia® bottles on D30.
No difference in concentration greater than 5% from the RC was observed in the drops extracted from LDPE bottles or in the drops extracted from Novelia® bottles for the 2 concentrations. Likewise, no difference in concentration greater than 5% from the RC was observed for the residual solutions of the 2 types of bottles on D30. The atropine concentration in drops extracted from Novelia® bottles was not significantly different from that of drops from LDPE bottles for the 2 concentrations (p-value = 0.74 atropine 0.1 mg.mL-1; p-value= 0.64 atropine 0.5 mg.mL-1). All of the BactAlert® performed on the residual solutions of Novelia® bottles on D30 were negative.
There is no interaction between atropine and the different materials of Novelia® system. The sterility of eye drops packaged in Novelia® bottles is maintained for up to 30 days after opening in simulated use conditions. Novelia® bottles are suitable for packaging atropine eye drops at 0.1 mg / mL and 0.5 mg / mL.