Cold flow of estradiol transdermal systems: influence of drug loss on the in vitro flux and drug transfer across human epidermis. Academic Article uri icon


  • The objective was to quantify drug loss due to cold flow (CF) in marketed estradiol transdermal drug delivery systems (TDDS), and study its influence on the in vitro flux and drug transfer across contacting skin. TDDS samples (products-A and B) were induced with CF at 25 and 32C/60% RH by applying 1-kg force for 72h. CF was measured as percent dimensional change and amount of drug loss/migration in CF region. In vitro drug permeation studies were conducted across human epidermis from TDDS excluding CF region, and CF region alone against control (without CF). In both products, significantly higher percentage of CF (dimensional change and drug migration) was observed at 32C compared to 25C. In vitro flux from both products excluding CF region either at 25 or 32C was the same, but significantly lower compared to control. Drug transferred from CF region of product-A after 8h was the same at 25 and 32C, but significantly higher in product-B. Flux from both products together with CF region at 32C was significantly lower than that observed at 25C. Results showed that excessive CF at storage (25C) and clinical usage (32C) conditions may have implications on product performance and safety of estradiol TDDS.

published proceedings

  • Int J Pharm

author list (cited authors)

  • Krishnaiah, Y., Yang, Y., Hunt, R. L., & Khan, M. A.

citation count

  • 3

complete list of authors

  • Krishnaiah, Yellela SR||Yang, Yang||Hunt, Robert L||Khan, Mansoor A

publication date

  • December 2014