NOVEL SILICONES FOR TRANSDERMAL THERAPEUTIC SYSTEM .6. PREPARATION OFOLIGODIMETHYLSILOXANE CONTAINING 2-PYRROLIDONE MOIETY AS A TERMINAL GROUP AND ITS ENHANCING EFFECT ON TRANSDERMAL DRUG PENETRATION

Oligodimethylsiloxanes (ODMSs) containing a 2-pyrrolidone moiety at on e chain end were prepared to develop a silicone-based transdermal pene tration enhancer. The 1-alkyl-2-pyrrolidon-3-yl group was introduced a s a terminal group of ODMS via the initiator method, i.e., the anionic ring-opening polymerization of hexamethylcyclotrisiloxane was initiat ed with the silanolate anion derived from (1-alkyl-2-pyrrolidon-3-ylme thyl)dimethyl-silanol. The disiloxanes were also prepared from the sil anol derivatives by reaction with chlorotrimethylsilane. The enhancing activity of drug penetration was evaluated by in vitro experiments us ing a two-chamber diffusion cell. Indomethacin and antipyrine were use d as model drugs, and the amounts of drugs permeating through the rabb it abdominal skin were measured with and without the ODMSs or disiloxa nes. The enhancing activities are influenced by the chain length of th e siloxane components and the chemical structure of their end groups. A suitable balance between the hydrophobic ODMS chain and the polar en d group might be decisive for a high enhancing activity of drug penetr ation.