In-vitro release and transdermal fluxes of a highly lipophilic drug and of enhancers from matrix TDS

• Published in: Journal of controlled release Vol. 82; no. 1; pp. 63 - 70
• Main Authors: Funke, Adrian Peter, Günther, Clemens, Müller, Rainer Helmut, Lipp, Ralph
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 18.07.2002; Elsevier
• Subjects: Administration, Cutaneous; Animals; Antiestrogen; Biological and medical sciences; Drug Delivery Systems; Estradiol - administration & dosage; Estradiol - analogs & derivatives; Estradiol - pharmacokinetics; Estrogen Receptor Modulators - administration & dosage; Estrogen Receptor Modulators - pharmacokinetics; General pharmacology; Highly lipophilic drug; In Vitro Techniques; Lauric acid; Lauric Acids - administration & dosage; Lauric Acids - pharmacokinetics; Male; Medical sciences; Mice; Mice, Hairless; Permeability; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Propylene glycol; Propylene Glycol - administration & dosage; Propylene Glycol - pharmacokinetics; Skin - chemistry; Skin - metabolism; Skin Absorption; Sulfur Compounds; Transdermal drug delivery systems; Highly lipophilic drug; Propylene glycol; Transdermal drug delivery systems; Lauric acid; Antiestrogen; Delivery system; Transdermal system; Pharmaceutical technology; Rodentia; Permeation; Drug adjuvant; In vitro; Vertebrata; Mammalia; Acrylate polymer; Mouse; Animal; Skin; Absorption enhancer; Propanediol; Release; Physicochemical properties; Topical administration
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/S0168-3659(02)00105-0

Transdermal systems (TDS) are a well-known application form for small, moderately lipophilic molecules. The aim of this study was to investigate the possibility of applying a highly lipophilic drug, the antiestrogen AE (log P=5.82) transdermally by polyacrylate-based matrix TDS. For this purpose, two effects of both drug and enhancer concentration in TDS were investigated: in-vitro release and transdermal permeation of drug and enhancers. In the TDS investigated, in-vitro release as well as in-vitro permeation of AE through excised skin of hairless mice was found to be independent of concentrations of both drug and enhancers. The steady-state fluxes observed were low (about 50–100 ng cm −2 h −1). But skin pretreatment with permeation enhancers resulted in a markedly enhanced permeability (1400 ng cm −2 h −1). Therefore, the permeation of this highly lipophilic drug seems to be limited by the stratum corneum barrier function. In contrast, the transdermal permeation of the enhancers was dependent on the TDS composition. Increase in enhancer content resulted in a higher permeation of enhancers, whereas skin pretreatment did not. In conclusion, it was shown that the highly lipophilic antiestrogen can be administered transdermally by pretreating the skin with the fluid permeation enhancer combination propylene glycol–lauric acid (9+1) and then applying a matrix TDS.