Enhancement of transdermal delivery of progesterone using medium-chain mono and diglycerides as skin penetration enhancers.
We evaluated whether medium-chain mono and diglycerides (MCG) can be utilized to optimize the transdermal delivery of progesterone (PGT). MCG was studied at 10-70% (w/w) in propylene glycol (a polar solvent) or Myvacet oil (nonpolar solvent); PGT was used at 1% (w/w). The topical (to the skin) and transdermal (across the skin) delivery of PGT were evaluated in vitro using porcine ear skin. When incorporated in propylene glycol, MCG at 10% enhanced the topical and transdermal delivery of PGT by 2.5- and 7-fold, respectively. At 20-50%, topical delivery was further enhanced while transdermal delivery gradually returned towards baseline. At 70%, MCG enhanced neither the delivery to viable skin nor the transdermal delivery of PGT. Similar concentration-dependent effects were observed when MCG was incorporated in Myvacet oil, but their magnitudes were 2- to 3-fold smaller. The relative safety of MCG was assessed in cultured fibroblasts and compared to propylene glycol (regarded as safe) and sodium lauryl sulfate (moderate-to-severe irritant). Both MCG and propylene glycol were substantially less cytotoxic than sodium lauryl sulfate. We conclude that formulations containing 10% MCG in propylene glycol may be a simple and safe method to improve the transdermal delivery of progesterone and promote its use in hormone replacement therapy.
Lopes
Luciana B
LB
Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
Murphy
Neal
N
Nornoo
Adwoa
A
D000279:Administration, Cutaneous; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005989:Glycerides / Q000494:pharmacology*; D051379:Mice; D050178:Monoglycerides / Q000494:pharmacology*; D011374:Progesterone / Q000008:administration & dosage*; D019946:Propylene Glycol; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects*; D013552:Swine; D041701:Swiss 3T3 Cells
D005989:Glycerides; D050178:Monoglycerides; D011374:Progesterone; D019946:Propylene Glycol