Transdermal delivery of hydrophobic and hydrophilic local anesthetics from o/w and w/o Brij 97-based microemulsions.
OBJECTIVE
To characterize the physicochemical properties of drug-loaded oil-in-water (o/w) and water-in-oil (w/o) Brij 97-based microemulsions in comparison to their blank counterparts and to investigate the influence of microemulsion type on in vitro skin permeation of model hydrophobic drugs and their hydrophilic salts.


METHODS
The microemulsion systems were composed of isopropyl palmitate (IPP), water and a 2:1 w/w mixture of Brij 97 and 1-butanol. The samples were characterized by visual appearance, pH, refractive index, electrical conductivity, viscosity and determination of the state of water and IPP in the formulations using differential scanning calorimetry (DSC). Transdermal flux of lidocaine, tetracaine, dibucaine and their respective hydrochloride salts through heat-separated human epidermis was investigated in vitro using modified Franz diffusion cells.


RESULTS
The physicochemical properties of drug-loaded microemulsions and their blank counterparts were generally similar; however, slight changes in some physicochemical properties (apparent pH and conductivity) were observed due to the intrinsic properties of the drugs. The o/w microemulsions resulted in the highest flux of lidocaine, tetracaine and dibucaine as compared to the other formulations with in the same group of drugs.


CONCLUSIONS
The characterization results showed that incorporation of the model drugs into the microemulsions did not change the microemulsion type. The permeation data exhibited that the nature of the microemulsions was a crucial parameter for transdermal drug delivery. The o/w microemulsions containing hydrophobic drugs provided the highest skin permeation enhancement. In addition, skin permeation was depended on the molecular weight of the model drugs.
Junyaprasert
Varaporn Buraphacheep
VB
Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand. pyvbp@mahidol.ac.th
Boonme
Prapaporn
P
Songkro
Sarunyoo
S
Krauel
Karen
K
Rades
Thomas
T
D020001:1-Butanol / Q000737:chemistry; D000279:Administration, Cutaneous; D000779:Anesthetics, Local / Q000493:pharmacokinetics*; D002152:Calorimetry, Differential Scanning; D003992:Dibucaine / Q000493:pharmacokinetics; D004553:Electric Conductivity; D004655:Emulsions; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D008012:Lidocaine / Q000493:pharmacokinetics; D008970:Molecular Weight; D010168:Palmitates / Q000737:chemistry; D010539:Permeability; D010938:Plant Oils / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012869:Skin Absorption; D013748:Tetracaine / Q000493:pharmacokinetics; D014783:Viscosity; D014867:Water / Q000737:chemistry
D000779:Anesthetics, Local; D004655:Emulsions; D010168:Palmitates; D010938:Plant Oils; D014867:Water; D013748:Tetracaine; D011092:Polyethylene Glycols; C005060:isopropyl palmitate; D020001:1-Butanol; C033084:polyethylene glycol oleyl ether; D008012:Lidocaine; D003992:Dibucaine