Topical delivery of N-alkyl-N-alkyloxycarbonylaminomethyl (NANAOCAM) prodrugs of theophylline (ThH).

N(7)-(N-Alkyl-N-alkyloxycarbonyl) aminomethyl (NANAOCAM) prodrugs of theophylline (ThH) have been synthesized and characterized by their solubilities in isopropyl myristate (S(IPM)), solubilities in water (S(AQ)), partition coefficients between IPM and pH 4.0 buffer (K(IPM:4.0)) and by their ability to penetrate hairless mouse skin from IPM (J(MIPM)). The most lipid soluble and water soluble member, N-methyl-N-ethyloxy-carbonylaminomethyltheophylline, gave the highest flux through hairless mouse skin from IPM compared to ThH. The flux of NANAOCAM prodrugs of ThH can be accurately predicted by the Roberts-Sloan (RS) equation.