John B. Glen spent 13 years perfecting propofol; for his efforts, he was recently honoured with the 2018 Lasker Award for clinical research.
Propofol, in a form solubilized in cremophor EL, was first identified as a drug candidate in 1973 and began clinical trials in 1977.Cremophor caused anaphylactic reactions, so this formulation was taken off the market and replaced with a soy oil and propofol emulsion in water.
In 1986, Imperial Chemical Industries (whose pharmaceutical division later became part of AstraZeneca) reintroduced the emulsified formulation under the brand name Diprivan. The current preparation contains 1% propofol, 10% soybean oil, 1.2% purified egg phospholipid as an emulsifier, 2.25 % glycerol as a tonicity-adjusting agent, and sodium hydroxide to adjust the pH. Diprivan’s active ingredient, EDTA, is a common chelating agent that also exhibits activity both independently (bacteriostatically against some bacteria) and in concert with other antimicrobials. Sodium metabisulfite and benzyl alcohol are used as antimicrobial agents in modern generic formulations. Light is scattered by the tiny oil droplets in propofol emulsion (about 150 nm), making the fluid appear very opaque and white in colour.
Fospropofol, a prodrug form that dissolves easily in water, has shown promising results in testing. The enzyme alkaline phosphatase quickly converts fospropofol into propofol. This newer formulation, marketed under the brand name Lusedra, may reduce or eliminate the injection site pain associated with the original drug. The FDA of the United States gave its blessing to the product in 2008.
Adding lidocaine to propofol for IV analgesia is a common practise, despite the fact that mixing drugs is not recommended. Oil droplets may coalesce when lidocaine and propofol are combined, which increases the possibility of a pulmonary embolism.
Cyclodextrins are used as a solubilizing agent in another nonlipid formulation of propofol. Guests (propofol) and hosts (cyclodextrins) form complexes that move back and forth between the hydrophilic core of the cyclodextrin molecule and the aqueous environment. This makes it possible to inject propofol, which is only slightly soluble in water. After injection, the propofol leaves the cyclodextrin and enters the bloodstream. The public release of this formulation is pending the results of ongoing clinical trials.
