Construction of a quantitative structure-permeability relationship (QSPR) for the transdermal delivery of NSAIDs.
In this study, an empirical model of the quantitative structure-permeability relationship (QSPR) of the transdermal delivery of non-steroidal anti-inflammatory drugs (NSAIDs) was constructed in an attempt to predict the permeability coefficients (k(P)). Thirteen model NSAIDs were selected, and their in vitro permeation through the full skin of nude mice was examined. The biological parameters of transepidermal water loss (TEWL), hydration content (HD), lipid content (SB), resonance running time (RVM), and elasticity (EL) were measured. The permeability coefficients so obtained were grouped into three datasets of all model drugs and those drugs with clogP or logK(o/w) values of >2 and <2; these datasets were regressed with respect to the physical characters of molecular weight (MW) and polarity factor (clogP or logK(o/w)) or the solubility parameter (delta) of the model drugs rationally chosen to replace the polarity factor with or without taking into consideration the biological parameters of the skin. Results demonstrated that delta could be greatly improved compared to clogP and logK(o/w) in the regression with an adjusted R(2) of >0.90 using the dataset of those drugs with clogP or logK(o/w) values of <2, regardless of whether or not biological parameters were taken into consideration. This indicates that delta might rationally be a more-appropriate drug parameter for predicting the skin permeability of NSAIDs for transdermal delivery. A plot of observed k(P) versus predicted k(P) values by this simple empirical model of QSPR was validated to demonstrate the predictive capability of k(P) for transdermal delivery. In conclusion, an empirical model of QSPR to predict k(P) based on the hydrophilicity of the model drugs was statistically improved with delta and by taking the biological parameters of the skin into consideration.
Liou
Yi-Bo
YB
College of Pharmacy, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan, ROC.
Ho
Hsiu-O
HO
Yang
Chun-Jen
CJ
Lin
Ying-Ku
YK
Sheu
Ming-Thau
MT
D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D010539:Permeability; D021281:Quantitative Structure-Activity Relationship; D012867:Skin / Q000378:metabolism*; D012995:Solubility
D000894:Anti-Inflammatory Agents, Non-Steroidal