NOVEL SILICONES FOR TRANSDERMAL THERAPEUTIC SYSTEM .4. MODIFIED ROUTE TO PREPARE OLIGODIMETHYLSILOXANE CONTAINING A CATIONIC END-GROUP, AND ITS PROPERTY AS TRANSDERMAL PENETRATION ENHANCER

A 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.