A novel skin penetration enhancer: evaluation by membrane diffusion and confocal microscopy.
OBJECTIVE
The aim of this study was to determine the in vitro transdermal efficacy of a Meyer Zall Laboratories (MZL) oil/water emulsion in two separate preparations containing the actives, coal tar and the non-steroidal anti-inflammatory drug, diclofenac sodium.


METHODS
The release rate of the two active ingredients from MZL dermatological preparations, Exorex and Athru-Derm and four comparator products was determined using an enhancer cell system, whilst specific penetration characteristics of the MZL formulation were elucidated using confocal and electron microscopy. The latter properties were explored at both the organ level, using human skin, as well as at a cellular level using a melanoma cell line.


RESULTS
While the in vitro release rates for all formulations was high, coal tar and diclofenac release from Exorex and Athru-Derm respectively was, at nearly all time intervals, significantly higher than from comparator products. Microscopy revealed the presence of spherical liposomal type structures in both the MZL lotion and a comparator gel. In the MZL lotion, the majority of these structures, referred to here as emzaloid particles, were in the order of magnitude of about 50 nm to 1 microm in diameter with a small minority exceeding these dimensions. After application of Athru-Derm to human skin, intact emzaloid particles of submicron dimensions were detected in the epidermis in association with the cell membranes. The affinity of the MZL lotion for cell membranes was further demonstrated with melanoma cells; in addition, the formulation was seen to penetrate even to the nucleus of viable cells.


CONCLUSIONS
Overall the data suggest that the oil/water base in MZL formulations is a highly efficient transdermal vehicle able to transport a wide range of indication- specific actives to their site of action.
Saunders
J
J
Meyer Zall Laboratories, Drie Valleyen, Sedgefield, South Africa. jcjs@mzl.co.za
Davis
H
H
Coetzee
L
L
Botha
S
S
Kruger
A
A
Grobler
A
A
D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics; D002417:Cattle; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D003033:Coal Tar / Q000008:administration & dosage / Q000493:pharmacokinetics; D004008:Diclofenac / Q000008:administration & dosage / Q000493:pharmacokinetics; D004058:Diffusion; D004337:Drug Carriers; D004643:Emollients / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004655:Emulsions; D005079:Excipients / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007641:Keratolytic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D008081:Liposomes; D008545:Melanoma / Q000378:metabolism; D018613:Microscopy, Confocal; D012869:Skin Absorption / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D004643:Emollients; D004655:Emulsions; D005079:Excipients; D007641:Keratolytic Agents; D008081:Liposomes; D004008:Diclofenac; D003033:Coal Tar