Towards a correlation between drug properties and in vitro transdermal flux variability.
Over recent years, there has been growing evidence that the permeability coefficient variability describing any specific transdermal drug delivery system is not always normally distributed. However, since different researchers have used different test compounds, methodologies and skin types, it has been difficult to identify any general correlation between drug properties and flux variability. The aim of the present study was to investigate whether there was a relationship between these two variables. To this end, six different compounds (sucrose, adenosine, aldosterone, corticosterone, oestradiol and testosterone) exhibiting a range of partition coefficients but relatively similar molecular weights were screened by taking multiple replicate measurements of their permeation profiles as they penetrated across porcine skin in vitro. It was found that for relatively hydrophilic solutes (log P(o/w)< or = approximately 2.5), physicochemical properties that facilitated slow transdermal flux were associated with more positively skewed permeability coefficient distributions while rapid flux was associated with more symmetric distributions. However, no correlation could be found between molecular properties and the extent of statistical fit to either the normal or log-normal distribution.
Frum
Yakov
Y
Division of Pharmaceutical Sciences, University of Strathclyde, SIPBS, 27 Taylor Street, Glasgow G4 0NR, Scotland, UK.
Khan
Gul M
GM
Sefcik
Jan
J
Rouse
Jennifer
J
Eccleston
Gillian M
GM
Meidan
Victor M
VM
D000450:Aldosterone / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001692:Biological Transport; D003345:Corticosterone / Q000737:chemistry / Q000493:pharmacokinetics; D004958:Estradiol / Q000737:chemistry / Q000493:pharmacokinetics; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D007700:Kinetics; D016014:Linear Models; D008970:Molecular Weight; D016011:Normal Distribution; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D010599:Pharmacokinetics; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D016008:Statistical Distributions; D013395:Sucrose / Q000737:chemistry / Q000493:pharmacokinetics; D013552:Swine; D013739:Testosterone / Q000737:chemistry / Q000493:pharmacokinetics; D013997:Time Factors
D004364:Pharmaceutical Preparations; D013739:Testosterone; D000450:Aldosterone; D004958:Estradiol; D013395:Sucrose; D003345:Corticosterone