Novel lipid and preservative-free propofol formulation: properties and pharmacodynamics.
OBJECTIVE
Propofol is a water-insoluble intravenous anesthetic agent that is actually formulated as a water-in-oil emulsion with known drawbacks such as pain on injection, microorganism growth support and stability. We report on the properties of formulations of propofol in poly (N-vinyl-2-pyrrolidone)-block-poly(D,L-lactide), PVP-PLA, polymeric micelles (Propofol-PM).


METHODS
Microbial growth in these formulations was evaluated with Pseudomonas aeruginosa (ATCC 9027), Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 25922) and Candida albicans (ATCC 10231). Sleep-recovery studies in female Sprague-Dawley rats, at a dose of 10mg/kg were performed to compare pharmacodynamic profiles of the new Propofol-PM formulations with those of Diprivan, a commercially available lipid based propofol formulation.


RESULTS
Growth of microorganisms was not supported in the Propofol-PM formulations tested. No significant differences in times to unconsciousness, awakening, recovery of righting reflex and full recovery were observed between Propofol-PM formulations and Diprivan.


CONCLUSIONS
Propofol loaded in PVP-PLA micelles (Propofol-PM) is not significantly different in terms of pharmacodynamic but demonstrates no microorganism growth support and improved stability that opens up the door to pain on injection reduction strategy.
Ravenelle
François
F
Labopharm Inc., 480 Blvd. Armand-Frappier, Laval, Québec, Canada, H7V 4B4. fravenelle@labopharm.com
Gori
Sandra
S
Le Garrec
Dorothée
D
Lessard
David
D
Luo
Laibin
L
Palusova
Dana
D
Sneyd
J Robert
JR
Smith
Damon
D
D000818:Animals; D002626:Chemistry, Pharmaceutical; D015169:Colony Count, Microbial; D004355:Drug Stability; D005260:Female; D010316:Particle Size; D015742:Propofol / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects
D015742:Propofol