Novel silicones for transdermal therapeutic system, 4. Modified route to prepare oligodimethylsiloxane containing a cationic end‐group, and its property as transdermal penetration enhancer

Abstract

AbstractA modified route to prepare oligodimethylsiloxane (ODMS) containing a quaternary salt at the one chain end was investigated, for the development of a silicone‐based transdermal penetration enhancer. p‐(Chloromethyl)phenethyl‐terminated ODMS (CMP‐ODMS) was prepared by hydrosilylation of p‐chloromethylstyrene with hydrosilyl‐terminated ODMS, as an intermediate. Then, CMP‐ODMS was reacted with pyridine or ethyldimethylamine to afford a quaternary ODMS salt quantitatively. The enhancing activity of drug penetration was evaluated by measuring the amount of indomethacin permeating through the skin, using a two‐chamber diffusion cell having an isolated rabbit abdominal skin mounted between half cells. The obtained polymers effectively enhanced the drug penetration through the skin, whereupon the permeation coefficients were 2 to 15 times that measured without enhancer. Also, the enhancing activities were influenced by the chemical structure of polar and non‐polar end‐groups.