Hospital production of a 1% propofol–cyclodextrin formulation to address drug shortages: a proof of concept

OBJECTIVES: Drug shortages, particularly in anaesthesia, pose a risk to patient care. Propofol, a widely used anaesthetic, is formulated as an emulsion requiring a complex industrial manufacturing and pharmaceutical supply chain, making propofol vulnerable. Cyclodextrins can enhance the aqueous solubility of lipophilic drugs and may provide an alternative approach. The objective of this study was to develop and evaluate a ready-to-use cyclodextrin-based propofol formulation that could be prepared in a hospital pharmacy using standard equipment. METHODS: A 1% (w/v) propofol solution was prepared using hydroxypropyl-β-cyclodextrin (HP-β-CD). The association constant (Ka) was calculated using the Higuchi and Connors method. The solution was sterilised by 0.22 µm filtration or by autoclaving at 121°C for 15 min. Stability was assessed over 90 days at 2-8°C and 20-25°C. A validated HPLC-UV method was used to quantify propofol and detect degradation products. Additional quality controls included pH, osmolality, subvisible particles, sterility and endotoxin levels. RESULTS: The Ka was 1288±32 M⁻¹. A clear 1% (w/v) solution was obtained with 17% (w/v) HP-β-CD and 0.35% (w/v) sodium chloride, without pH adjustment. Both sterilisation methods preserved drug integrity. The formulation remained stable for 3 months under refrigeration. At room temperature, degradation occurred after 14 days. CONCLUSION: This study demonstrates the feasibility of a hospital-based preparation of a sterile injectable propofol solution using cyclodextrins. These results support the role of hospital pharmacies in addressing drug shortages by enabling locally controlled and resilient production capacity.