Stability of oxycodone solutions containing S-ketamine or dexmedetomidine

Abstract

<p><strong>Objectives</strong> To determine whether adding <em>S-</em>ketamine or dexmedetomidine to oxycodone affects the microbiological, physical or chemical stability of patient-controlled analgesia (PCA) solutions prepared in a hospital pharmacy.</p><p><strong>Methods</strong> Oxycodone solution (1 mg/mL) and three oxycodone–<em>S-</em>ketamine mixtures (0.25, 0.50, 0.75 mg/mL) and three oxycodone–dexmedetomidine mixtures (2.5, 5.0, 10 µg/mL) were compounded under validated European Union Good Manufacturing Practice (GMP) Class A/B aseptic conditions and filled into PCA reservoirs. Reservoirs (n=42 for physicochemical studies, n=21 for sterility, n=4 for antimicrobial activity testing) were stored at 2–8°C for 28 days, then at 20–25°C for 2 days. Sterility was assessed by membrane filtration according to European Pharmacopoeia Section 2.6.1 (Ph. Eur. 2.6.1). Physical stability was evaluated by visual inspection, pH, weight and osmolality. Chemical stability was assessed using a validated high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method developed in accordance with US Food and Drug Administration (FDA) and International Conferenece on Harmonisation (ICH) Q2(R1) guidelines.</p><p><strong>Results</strong> All antimicrobial activity tests showed growth of the six reference strains, indicating no inhibition by the drug mixtures. All 21 sterility-test reservoirs remained free of turbidity throughout 30 days. No visual changes, precipitation or discolouration were observed. Weight loss was ≤0.3%, pH changes were within the required range of 4.5–7 and osmolality increased by <1.4% during the study. Measured oxycodone, <em>S-</em>ketamine and dexmedetomidine concentrations remained within ±5% of initial values, and no degradation products were detected.</p><p><strong>Conclusions</strong> Oxycodone PCA solutions containing <em>S-</em>ketamine or dexmedetomidine remained sterile, physically stable and chemically stable for 28 days at 2–8°C followed by 2 days at room temperature at 20–25°C. These findings support the potential for extended shelf life and centralised batch preparation of opioid–adjuvant PCA reservoirs in hospital pharmacy practice.</p>