Novel silicones for transdermal therapeutic system .6. Preparation of oligodimethylsiloxane containing 2-pyrrolidone moiety as a terminal group and its enhancing effect on transdermal drug penetration

Oligodimethylsiloxanes (ODMSs) containing a 2-pyrrolidone moiety at one chain end were prepared to develop a silicone-based transdermal penetration enhancer. The 1-alkyl-2-pyrrolidon-3-yl group was introduced as a terminal group of ODMS via the initiator method, i.e., the anionic ring-opening polymerization of hexamethylcyclotrisiloxane was initiated with the silanolate anion derived from (1-alkyl-2-pyrrolidon-3-ylmethyl)dimethyl-silanol. The disiloxanes were also prepared from the silanol derivatives by reaction with chlorotrimethylsilane. The enhancing activity of drug penetration was evaluated by in vitro experiments using a two-chamber diffusion cell. Indomethacin and antipyrine were used as model drugs, and the amounts of drugs permeating through the rabbit abdominal skin were measured with and without the ODMSs or disiloxanes. The enhancing activities are influenced by the chain length of the siloxane components and the chemical structure of their end groups. A suitable balance between the hydrophobic ODMS chain and the polar end group might be decisive for a high enhancing activity of drug penetration.