Synthesis and transdermal penetration of stavudine-5'-esters.
The aim of this study was to investigate the effects of different ester groups in position 5' of stavudine on the transdermal penetration with and without the use of Pheroid™ as the delivery system. Six esters were prepared by reaction of stavudine with six different acid chlorides at room temperature. Female human abdominal skin was used for in vitro penetration in Franz diffusion cells. The experimental aqueous solubility of stavudine (104.75 mg/mL) was much higher than that of the synthesized derivatives (ranging from 0.08 to 5.17 mg/mL), while the log D (octanol-buffer partition coefficient) of stavudine (-0.85) was lower than that of its derivatives (ranging from -0.41 to 3.06). The experimental transdermal flux of stavudine (6.52 µmol/cm(2).h) in PBS (phosphate buffer solution) was much higher than that of any of its derivatives (0.06 - 0.23 µmol/cm(2).h), while the propionyl (6.64 µmol/cm(2).h) and the butyryl esters (6.87 µmol/cm(2).h) had the highest transdermal flux using the Pheroid™ (0.75 - 6.87 µmol/cm(2).h) system.
Pharmaceutical Chemistry, Unit for Drug Research and Development, North-West University, Potchefstroom 2520, South Africa.
Estée-Marie
EM
Holmes
Jaco C
JC
Breytenbach
Minja
M
Gerber
Jeanetta
J
du Plessis
D000279:Administration, Cutaneous; D055598:Chemical Phenomena; D004058:Diffusion; D016503:Drug Delivery Systems; D004951:Esterification; D004952:Esters / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006801:Humans; D010539:Permeability; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D012995:Solubility; D018119:Stavudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology
D004952:Esters; D018119:Stavudine