The use of patient-controlled analgesia (PCA) allows patients to self-administer bolus doses or maintain a continuous flow of analgesics, which may increase the quality of life of patients. The problems caused by the increased use of opioids have increased interest in enhancing pain management with adjuvants. The aim of this study was to investigate how the addition of adjuvant, S-ketamine or dexmedetomidine, affects the microbiological and physicochemical stability of the oxycodone solution used in PCA.

Oxycodone solution as well as three different mixtures containing oxycodone and dexmedetomidine or oxycodone and S-ketamine were filled to PCA reservoirs in controlled and validated aseptic conditions and investigated. PCA reservoirs were stored in a refrigerator approved for hospital use (2–8 °C) for 28 days. Thereafter they were transferred to room temperature (20–25 °C) for 2 days. Samples for analysis were taken at predetermined intervals under aseptic conditions. Microbiological stability was assessed by performing a sterility test with the technique of membrane filtration as described in the European Pharmacopoeia. Physicochemical stability of the PCA solutions was studied by visual inspection and monitoring changes in pH, weight and osmolality during the study period. A high-performance liquid chromatography (HPLC) method was developed to test the chemical stability of PCA solutions.

All microbiological samples taken for the sterility test were clean over the study period. All solutions were initially clear and colourless and remained unchanged over the study period. No physical changes, such as visible particles, discoloration, opalescence, precipitation or gas formation were observed in any test solution. There was no clinically significant change in pH, weight and osmolality values of any PCA solution during the study period. The presumed drug concentrations were detected in all PCA reservoirs. The drug concentration levels remained almost unchanged during the study period. In all PCA reservoirs, changes in the drug concentration were less than 5% from the initial concentrations. No traces of degradation products were observed. The study results demonstrate that the studied oxycodone, S-ketamine and dexmedetomidine drug solutions and mixtures in PCA reservoirs prepared aseptically under controlled and validated conditions remain stable and sterile at 2–8 °C for at least 28 days and thereafter at room temperature (20–25 °C) for at least 2 days.