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

N7-(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. (c) 2006 Elsevier B.V. All rights reserved.