Microbiological stability study of Atropine 0.01% eye drops in LDPE packaging to produce hospital preparations

Severe juvenile myopia is prone to ocular complications that can prevented by 0.01% atropine eye drops. The duration of treatment of our cohort means that batch production must be adapted. Our current shelf-life is one month sealed and 4 days after opening. To optimize manufacturing, we need to seek longer stability, in real-life conditions and during a 3-month storage period.

Preparation of 2 batches of 30 atropine 0.01% eye drops from Atropine single doses 1% FAURE diluted 1:100 with BSS. These two batches, packaged in LDPE vials containing 10ml of solution, were prepared according to the guidelines for sterile preparations set out in the BPP, by aseptic distribution with sterilizing filtration. Batches were stored at room temperature for 3 months, divided into three series. Microbiological tests were conducted using the Bact/ALERT^® technique. The 1st series consisted solely of sealed vials stored on shelves, with evaluation at D0, 30, 60, 90 and D104. The other two series were divided into two patient profiles: "clean patient" (no manipulation of the tip after opening) versus "dirty patient" (manipulation of the tip after opening). Sterility checks for these 2 groups were carried out at D0, D3, D7, D10 and D14. Several physico-chemical parameters were also monitored, including pH (EcoScan pH meter), osmolarity (VAPPRO pressure osmometer - Model 5600) and particle count (Hemocytometer chamber - ZEISS Axioscope 5).

Results at 2 months showed no contamination of the sealed vials. The sterility of the eye drops in the "clean patient" group was also maintained until D14, which was not the case in the "dirty patient" group, where Cutibacterium acnes was found as early as D0. Other commensal germs such as Staphylococcus epidermidis, warneri and saprophyticus were added at subsequent sterility controls. Furthermore, physico-chemical parameters vary much more markedly for eye drops in the "dirty patient" category.

The fact that the sterility of eye drops is not maintained in the event of non-compliance with hygiene rules leads us to reject the extension of the expiry date once the bottle has been opened. Although these are commensal germs of the user’s skin, for which the risk of infection seems unlikely, the stability of the solution is nevertheless altered, with a risk of loss of efficacy/tolerance. A reminder of proper handling procedures, in the form of a patient information sheet, seems essential. However, this is still insufficient, and would suggest that a new administration device with a much more desirable anti-contamination technology should be referenced. It should also be noted that the 2-month shelf-life sterility of eye drops has been maintained.