Feasibility study for a preparation of ceftazidime 20 mg/mL for intravitreal injection
14 October 2019A.Sourisseau1, S.Vandewoestyne1, E.Olivier1, M. Papin1, C.Herrencknecht2, N.Cormier1
1 UF Pharmacotechnie, Pharmacie Hôtel Dieu CHU Nantes, France
2 UFR Sciences Pharmaceutiques et Biologiques Nantes, France
Ceftazidime 20 mg/mL syringes for intravitreal injection are currently prepared extemporaneously in the operating room by a physician for the emergency treatment of endophthalmitis. In order to secure the preparation, the syringes will be prepared, controlled and stored at the pharmacy to provide the dispensing upon request.
The objective is to conduct a preliminary study of the stability of the ceftazidime solution at 20 mg/mL in polypropylene syringes at 3 different storage conditions.
Eighty-four syringes were prepared under isolator by reconstitution and dilution with 0.9% sodium chloride (NaCl 0.9%); of one vial of ceftazidime 2g. Twelve syringes were stored at room temperature, 24 syringes were stored between +2°C and +8°C and 48 syringes were stored at -20°C. Ceftazidime concentration was monitored by high performance liquid chromatography (HPLC) with a 255 nm UV detector. Degradation products, including pyridine, have also been quantified. The following criteria were also studied: pH, osmolarity, sterility.
At room temperature, the ceftazidime concentration measured at D2 is less than 90% of the initial concentration. The pyridine content exceeds the maximum permitted value (MPV) by the European Pharmacopoeia (>0.3%) from day 1. Between +2°C and +8°C, the measured ceftazidime concentration remains above 90% of the initial concentration until D10, but the pyridine content becomes higher than the MPV from D5 onwards. In the freezer, the concentration of ceftazidime in syringes remains almost constant until D20 and then slowly decreases until D60, while remaining within the tolerance range [90%-110%]. The pyridine content remains below the MPV throughout this period. The pH and osmolarity values remain constant over the entire period studied, regardless of storage conditions. Furthermore, no microbial growth was observed.
Ceftazidime 20 mg/mL solution in polypropylene syringes appears to be chemically stable for 60 days in the freezer. The pyridine content is the limiting factor for setting storage conditions and shelf life. A stability study will be conducted on syringes stored in the freezer to confirm the results.