The invention provides injectable formulations of propofol using N-methylpyrrolidone or 2-pyrrolidone as a solvent. Formulations of the invention are useful in all medical and veterinary indications when propofol is presently used. In addition, combinations of propofol and an appropriate toxin are useful for fast-acting, humane, veterinary euthanasia injectable compositions. N-methylpyrrolidone-propylene glycol formulations are inherently bacteriostatic, thereby eliminating one of the problems associated with currently available formulations.
An injectable formulation of a sedative hypnotic drug, such as the anesthetic drug propofol, that is pharmaceutically stable and demonstrates a reduced incidence of pain upon injection. The formulation of the present invention employs a sulfoalkyl ether cyclodextrin solubilizing and complexing excipient, such as CAPTISOL.RTM. cyclodextrin (sulfobutyl ether .beta.-cyclodextrin) to form a true aqueous solution and not a suspension. This formulation minimizes the allergic response and microbial contamination issues typically associated with propofol parenteral formulations. The present formulation may also reduce pain on injection as compared to the known emulsion type propofol formulations. The liquid formulation can be sterile filtered unlike emulsion-type formulations of sedative hypnotics. The liquid formulation can be lyophilized or otherwise dried to yield a solid formulation.
Sterile pharmaceutical compositions parenteral administration containing propofol in an oil-in-water emulsion additionally containing an amount of the preservative tromethamine sufficient to prevent signficant growth of microorganisms for at least 24 hours after extrinsic contamination.
An anesthetic is provided that includes a mixture of propofol, a tonicity agent, a substantially phospholipid-free emulsifying agent, a preservative such as benzyl alcohol, and water. This anesthetic is made by combining these components and then filtering the mixture of these components through a sterilizing filter. This anesthetic may be parenterally administered to both induce and maintain anesthesia in animals.
An anesthetic is provided that includes a mixture of propofol, a tonicity agent, a substantially phospholipid-free emulsifying agent, a preservative such as benzyl alcohol, and water. This anesthetic is made by combining these components and then filtering the mixture of these components through a sterilizing filter. This anesthetic may be parenterally administered to both induce and maintain anesthesia in animals.
The present invention provides aqueous pharmaceutical compositions containing a lipophilic therapeutic agent. In particular, the invention provides aqueous pharmaceutical compositions containing the compound 2,6-diisopropylphenol (propofol). Preferred compositions of the invention contain propofol in the presence of at least one block copolymer (for example, P188 or another poloxamer) and a polyethylene glycol (PEG). Compositions of the invention are preferably sterile or are readily sterilized (e.g., by autoclaving) and are suitable for parenteral administration to any animal, including humans. The compositions are also chemically and physically stable over a wide range of environmental conditions and for extended periods of time.