Evaluation of novel water soluble compositions of propofol for intravenous anesthesia.

Solubilizing propofol without lipid-associated risks-hyperlipidemia, microbial growth, and severe injection pain-remains a major formulation challenge spanning over four decades. Traditional lipid emulsions persist largely due to the difficulty of achieving high-capacity aqueous solubilization without compromising safety or stability. This study evaluates a fat-free, preservative-free aqueous 1% propofol formulation enabled by a novel PEG-carbohydrate-lipid conjugate, 3,3-oleoyl-monomethoxy-polyethyleneglycol (n = 12 mean) ether-propanediaminolactobionate ("DOPS-F02"), highlighting its efficiency as an advanced solubilizing excipient for intravenous delivery. Solubilization capacity was profiled alongside a 24-month GLP stability trial of 1% propofol with 2.3% DOPS-F02 in 5% dextrose (Type I glass vials). A fixed-dose combination with 0.11% lidocaine HCl was evaluated without increasing excipient concentration. Pharmacokinetic, pharmacodynamic, and nociceptive profiles (rat paw-flick/paw-lick model) were compared against commercial control (Fresofol). DOPS-F02 demonstrated exceptional solubilization efficiency, driving propofol aqueous solubility up to 80 mg/mL at a low 1:2.2 w/w drug-to-solubilizer ratio in 5% dextrose or saline. Autoclaving induced a reversible cloud-point phase transition, returning to a clear, isotropic state upon cooling. Over 24 months, potency remained within ±3% with total impurities below 0.3%. In vivo, DOPS-F02 achieved therapeutic equivalence to Fresofol (loss of righting reflex; sleep duration 7.73-7.83 min). Unlike typical non-lipid formulations that exacerbate injection pain, DOPS-F02 allowed seamless co-formulation with lidocaine without phase separation, mitigating pain to near-baseline levels. As a novel solubilization platform, DOPS-F02 resolves a multi-decade formulation hurdle, delivering a clear, lipid-free propofol system requiring only a 1:2.2 drug-to-solubilizer ratio that eliminates emulsion liabilities and injection pain.