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Preparation and anesthetic properties of propofol microemulsions in rats
Timothy E Morey1, Jerome H Modell, Dushyant Shekhawat
1Department of Anesthesiology, University of Florida, Gainesville, 32610, USA.
Background:
The lipophilicity of propofol has required dispersion in a soybean macroemulsion. The authors hypothesized that the anesthetic properties of propofol are preserved when reformulated as a transparent microemulsion rather than as a turbid macroemulsion and that the dose-response relation can be selectively modified by altering the microemulsion's surfactant type and concentration.
Methods:
Microemulsions of propofol were formulated using purified poloxamer 188 (3%, 5%, 7%), and sodium salt of fatty acids (C(8), C(10), C(12)) in saline and characterized using ternary/binary diagrams, particle sizing, and stability upon dilution. Rats received propofol (10 mg . kg(-1) . min(-1)) as either a microemulsion or a conventional macroemulsion to determine these end points: induction (dose; stunned; loss of lash reflex, righting reflex, withdrawal to toe pinch) and recovery (recovery of lash, righting, withdrawal reflexes). After a 14-day recovery period, rats were crossed over into the opposite experimental limb.
Results:
Forty-eight microemulsions (diameter, 11.9-47.7 nm) were formulated. Longer carbon chain length led to a marked increase in the volume of diluent necessary to break these microemulsions. All rats experienced anesthetic induction with successful recovery, although significantly greater doses of propofol were required to induce anesthesia with microemulsions irrespective of surfactant concentration or type than with macroemulsions. The sodium salt of C10 fatty acid microemulsion required the greatest dose and longest time for anesthetic induction.
Conclusion:
Propofol microemulsions cause induction in rats similar to that from macroemulsions. The surfactant concentration and type markedly affect the spontaneous destabilization and anesthetic properties of microemulsions, a phenomenon suggesting a mechanism whereby dose-response relation can be selectively modified.
Insights
Propofol microemulsions maintain anesthetic properties but require higher doses for induction compared to macroemulsions. Surfactant choice significantly influences propofol
Area of Science:
- Anesthesiology
- Pharmaceutical Sciences
- Materials Science
Background:
- Propofol's lipophilicity necessitates soybean macroemulsion formulation.
- Hypothesis: Propofol microemulsions preserve anesthetic properties and allow dose-response modification.
- Investigating transparent microemulsions versus turbid macroemulsions.
Purpose of the Study:
- Evaluate propofol microemulsions for anesthetic properties.
- Determine if microemulsion formulation affects propofol's dose-response relationship.
- Assess the impact of surfactant type and concentration on microemulsion stability and efficacy.
Main Methods:
- Formulated propofol microemulsions with varying poloxamer 188 and fatty acid salts.
- Characterized microemulsions using phase diagrams, particle sizing, and stability tests.
- Administered propofol microemulsions and macroemulsions to rats to assess anesthetic induction and recovery.
Main Results:
- Successfully formulated 48 propofol microemulsions (11.9-47.7 nm).
- Microemulsions required significantly higher propofol doses for anesthetic induction than macroemulsions.
- C10 fatty acid microemulsions showed the longest induction time and highest dose requirement.
Conclusions:
- Propofol microemulsions induce anesthesia similarly to macroemulsions in rats.
- Surfactant concentration and type critically influence microemulsion destabilization and anesthetic effects.
- Microemulsion formulation offers a pathway to selectively modify propofol's dose-response characteristics.
