Synthesis and transdermal properties of acetylsalicylic acid and selected esters.
The primary aim of this study was to determine the transdermal penetration of acetylsalicylic acid and some of its derivatives, to establish a correlation, if any, with selected physicochemical properties and to determine if transdermal application of acetylsalicylic acid and its derivatives will give therapeutic drug concentrations with respect to transdermal flux. Ten derivatives of acetylsalicylic acid were prepared by esterification of acetylsalicyloyl chloride with ten different alcohols. The experimental aqueous solubility, logD and transdermal flux values were determined for acetylsalicylic acid and its derivatives at pH 4.5. In vitro penetration was measured through excised female human abdominal skin in diffusion cells. The experimental aqueous solubility of acetylsalicylic acid (6.56 mg/ml) was higher than that of the synthesised acetylsalicylate derivatives (ranging from 1.76 x 10(-3) to 3.32 mg/ml), and the logD of acetylsalicylic acid (-0.85) was lower than that of its derivatives (ranging from -0.25 to 1.95). There was thus an inverse correlation between the aqueous solubility data and the logD values. The experimental transdermal flux of acetylsalicylic acid (263.83 nmol/cm(2)h) was much higher than that of its derivatives (ranging from 0.12 to 136.02 nmol/cm(2)h).
Gerber
Minja
M
Pharmaceutical Chemistry, School of Pharmacy, North-West University, Potchefstroom 2520, South Africa. fchmg@puknet.puk.ac.za
Breytenbach
Jaco C
JC
Hadgraft
Jonathan
J
du Plessis
Jeanetta
J
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000378:metabolism*; D001241:Aspirin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism*; D004952:Esters / Q000138:chemical synthesis / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D012869:Skin Absorption; D012995:Solubility; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004952:Esters; D014867:Water; C028938:methyl acetylsalicylic acid; D001241:Aspirin