Phosphatidylcholine embedded micellar systems: enhanced permeability through rat skin.
Micellar and microemulsion systems are excellent potential vehicles for delivery of drugs because of their high solubilization capacity and improved transmembrane bioavailability. Mixtures of propylene glycol (PG) and nonionic surfactants with sodium diclofenac (DFC) were prepared in the presence of phosphatidylcholine (PC) as transmembrane transport enhancers. Fully dilutable systems with maximum DFC solubilization capacity (SC) at pH 7 are presented. It was demonstrated that the concentrates underwent phase transitions from reverse micelles to swollen reverse micelles and, via the bicontinuous transitional mesophase, into inverted O/W microstructures. The SC decreases as a function of dilution. DFC transdermal penetration using rat skin in vitro correlated with SC, water content, effect of phospholipid content, presence of an oil phase, and ethanol. Skin penetration from the inverted bicontinuous mesophase and the skin penetration from the O/W-like microstructure were higher than that measured from the W/O-like droplets, especially when the micellar system containing the nonionic surfactant, sugar ester L-1695, and hexaglycerol laurate. PC embedded within the micelle interface significantly increased the penetration flux across the skin compared to micellar systems without the embedded PC at their interface. Moreover, the combination of PC with HECO40 improved the permeation rate (P) and shortened the lag-time (T(L)).
Spernath
Aviram
A
Casali Institute of Applied Chemistry, The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Aserin
Abraham
A
Sintov
Amnon C
AC
Garti
Nissim
N
D000287:Administration, Topical; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004008:Diclofenac / Q000737:chemistry / Q000493:pharmacokinetics*; D015194:Diffusion Chambers, Culture; D016503:Drug Delivery Systems; D004655:Emulsions / Q000737:chemistry; D008297:Male; D008823:Micelles; D010539:Permeability / Q000187:drug effects; D044367:Phase Transition; D010713:Phosphatidylcholines / Q000737:chemistry*; D019946:Propylene Glycol / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D012995:Solubility; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry; D013997:Time Factors
D004655:Emulsions; D008823:Micelles; D010713:Phosphatidylcholines; D013501:Surface-Active Agents; D004008:Diclofenac; D019946:Propylene Glycol