Stability of ophthalmic preparations
EA 4676 C-Biosenss, UFR Pharmacie, Université d’Auvergne, Place Henri Dunant, 63001 Clermont-Ferrand
In-house pharmacies often have to make ophthalmic preparations (eye drops or injectable preparations) to overcome the lack of pharmaceutical specialities in the context of the treatment or prevention of ocular pathologies. To meet the increasing demand and/or to manage therapeutic emergencies, pharmacists are obliged to manufacture stocks of these sterile preparations. For that purpose, they have to define the optimal storage conditions and therefore need to have stability data available.
To obtain such data, the pharmacist either has to run a stability study of his preparations himself or refer to the bibliographic data available on the subject. In the first case, if he observes the required methodological rules, he will obtain information related to his preparation. In the case of a review of the literature, it is important to interpret the data with all due caution and to be wary of extrapolations. The preservation of a preparation may of course vary according to the conditions of conservation but also depending on other factors such as the formulation or the packaging. In interpreting stability data for an ophthalmic preparation, the following parameters must be taken into account: the formulation of the preparation (the nature of the excipients, the concentration in active principle, etc.), the type of container and the constituent materials, the preparation conditions (filtering, autoclaving, etc.) and conservation conditions (light, temperature, etc.).
The stability of an ophthalmic preparation is assessed according to the evolution in time of its physical, chemical and, as applies, microbiological parameters. Physical stability includes visual and olfactory data together with the tracing of invisible particles. To study the chemical stability of a preparation, the analysis method must be adapted and validated as Stability Indicating Methods. For that purpose, separation techniques are the methods of choice as they make it possible to achieve a separation and even a quantification of any degradation products. Monitoring of the concentration in active principle and the appearance of degradation products with time is completed by measurement of the pH and osmolality. In the case of a multi-dose preparation, or if the tight-sealing of the packaging cannot be guaranteed, the microbiological stability must be verified.
A few examples of the stability of ophthalmic preparations by in-house pharmacies evidence the importance of the criteria described above. Such is the case for intracamerular solutions of cefuroxime the stability of which varies depending on the conditions of temperature and packaging used in the case of freezing (syringe or glass bottle). The physical and chemical stability of ticarcillin depends on temperature and on the concentration in antibiotics. It would appear that repeated opening of multi-dose bottles also adversely affects the chemical stability of ticarcillin eye drops. Ophthalmic solutions of vancomycin can be frozen but the method of thawing and the conditions of conservation impact the stability of the preparation. The stability of cyclosporine eye drops has been validated in glass or polyethylene containers, but what happens when the drop counters are fitted to the bottle in the knowledge that cyclosporine migrates by absorption in the PVC? Finally, is it possible to envisage conservation of syringes of bevacizumab or of infliximab for several months by referring to the data currently available in the scientific literature?