Effect of PGML excipient mixture in a transdermal system on the in vitro transport of estradiol across skin.
OBJECTIVE
To measure the effect of a combination of excipients from a silicone based pressure sensitive adhesive (PSA) on drug transport across skin.


METHODS
Partitioning of propylene glycol monolaurate (PG-ML) from silicone PSA and a solution formulation into the stratum corneum (SC) was measured using radiolabeled PG-ML. Transport of a model drug, estradiol, as well as PG-ML across skin were measured in vitro using heat separated epidermis from human cadaver skin.


RESULTS
The PG-ML partitioning into SC showed a saturation and was independent of the formulation. The local dielectric of the lipid bilayers of the SC showed an increase as a result of PG-ML uptake, as determined by the decrease in fluorescence lifetime of a lipophilic probe incorporated into the SC. However, there was no alteration of lipid packing in SC.


CONCLUSIONS
The PG-ML and estradiol transport showed a good correlation over 3 days, suggesting that the two species are co-transported across the epidermis.
Irion
G D
GD
Cygnus Therapeutic Systems, Redwood City, California 94063, USA.
Garrison
M D
MD
Abraham
W
W
D000279:Administration, Cutaneous; D004958:Estradiol / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D005079:Excipients / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007848:Laurates / Q000494:pharmacology*; D011409:Propylene Glycols / Q000494:pharmacology*; D012828:Silicones / Q000737:chemistry / Q000494:pharmacology; D012867:Skin / Q000737:chemistry; D012869:Skin Absorption / Q000187:drug effects*; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics; D014014:Tissue Adhesives
D005079:Excipients; D007848:Laurates; D011409:Propylene Glycols; D012828:Silicones; D014014:Tissue Adhesives; C098387:propyleneglycol monolaurate; D004958:Estradiol