Development of matrix patches for transdermal delivery of a highly lipophilic antiestrogen.
The aim of this study was to develop matrix-type transdermal systems (TDSs) containing the highly lipophilic (log P = 5.82) antiestrogen (AE) and the permeation enhancers propylene glycol and lauric acid. For that purpose, permeation of AE from various adhesive matrices through excised skin of hairless mice was evaluated. It was found that pretreatment of the skin with permeation enhancers raised the transdermal flux of subsequently applied antiestrogen. Highest steady-state transdermal fluxes (1.1 microg cm(-2) h(-1)) were obtained from Gelva, polyacrylate adhesive, followed by 0.55 microg cm(-2) h(-1) from Oppanol polyisobutylene, 0.31 microg cm(-2) h(-1) from BIO-PSA silicone, and 0.12 microg cm(-2) h(-1) from Sekisui polyacrylate matrices. In order to develop TDS with high content of fluid permeation enhancer propylene glycol, two different strategies were investigated. One strategy was the addition of hydroxypropyl cellulose (HPC) as thickening agent to Gelva matrices. This allowed for propylene glycol loading levels of up to 30%, resulting in transdermal AE fluxes of 0.09 microg cm(-2) h(-1). On the other hand, a fleece-laminated backing foil was loaded with the described permeation enhancer formulation and laminated with polyacrylate adhesive layer, resulting in transdermal AE fluxes of 0.06 microg cm(-2) h(-1). However, application of these TDSs on skin pretreated with permeation enhancers raised the fluxes to 2.6 microg cm(-2) h(-1) from Gelva/HPC and 0.46 microg cm(-2) h(-1) from fleece/Sekisui.
Funke
Adrian Peter
AP
Pharmaceutical Development, Schering AG, Berlin, Germany.
Günther
Clemens
C
Müller
Rainer Helmut
RH
Lipp
Ralph
R
D000269:Adhesives / Q000627:therapeutic use; D000279:Administration, Cutaneous; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D020847:Estrogen Receptor Modulators / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D010539:Permeability / Q000187:drug effects; D019946:Propylene Glycol / Q000493:pharmacokinetics; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*; D013997:Time Factors
D000269:Adhesives; D020847:Estrogen Receptor Modulators; D019946:Propylene Glycol