Effect of PGML excipient mixture in a transdermal system on the in vitro transport of estradiol across skin.

To measure the effect of a combination of excipients from a silicone based pressure sensitive adhesive (PSA) on drug transport across skin. 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. 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. The PG-ML and estradiol transport showed a good correlation over 3 days, suggesting that the two species are co-transported across the epidermis.