Estradiol pharmacokinetics after transdermal application of patches to postmenopausal women: matrix versus reservoir patches

Abstract

Objective A new matrix 17β-estradiol transdermal patch incorporating lauric acid to improve estradiol skin absorption has been designed for hormone replacement therapy. Estradiol pharmacokinetics obtained with the prototype, its industrial counterpart, a matrix-type, Systen® 50, and a reservoir-type, Estraderm® TTS 50, transdermal patch have been compared. Each device delivers 50 μg estradiol daily.

Methods Twenty postmenopausal women received each of the four formulations for 3 days in a Latin-square design and with a minimum 4-day wash-out period between treatments. Estradiol plasma concentrations were measured by radioimmunoassay at 6, 12, 24, 48 and 72 h after application.

Results The prototype patch and its industrial counterpart showed no significant difference in estradiol delivery, with 72-h systemic exposure to estradiol similar to that of the reservoir patch but greater than that of the reference matrix formulation, with average baseline-corrected concentrations (SEM) of 35 (4), 32 (3), 32 (2) and 19 (1.8) pg/ml, respectively. In addition, they ensured more stable delivery, with coefficients of variation of plasma estradiol concentrations (12–72 h) of 29, 41, 63 and 84%, respectively. All matrix patches demonstrated the same patients to be poor estradiol absorbers, different from those encountered with the reservoir patch type, despite an improved estradiol bioavailability with the lauric acid-containing matrix patch.

Conclusion Matrix patches incorporating lauric acid led to estradiol plasma levels more stable than with the reference matrix and reservoir patches, and greater than those with the reference matrix patch.

Key Words:

• 17β-ESTRADIOL
• PHARMACOKINETICS
• HORMONE REPLACEMENT THERAPY
• TRANSDERMAL
• RESERVOIR
• MATRIX
• PATCHES
• ABSORBERS