NOVEL SILICONES FOR TRANSDERMAL THERAPEUTIC SYSTEMS .1. SYNTHESIS OF 1-METHYL-4-PYRIDINIO-TERMINATED POLYDIMETHYLSILOXANE AND EVALUATION AS A TRANSDERMAL PENETRATION ENHANCER

Alpha-(2-(4-pyridyl)ethyl)-polydimethylsiloxane (Py-PDMS) was prepared according to the anionic ring opening polymerization of hexamethylcyclotrisiloxane (D3) initiated with sodium 2-(4-pyridyl)ethyl-dimethylsilanolate, which were derived from the reaction of 2-(4-pyridyl)ethyl-dimethylsilanol with sodium hydride. The average degree of polymerization of Py-PDMS was controlled in the range between 3 and 34 by changing the ratio of D3 and the initiator. Furthermore, the preparation of alpha-(2-(1-methyl-4-pyridinio)ethyl)-polydimethylsiloxane (MePy-PDMS) was carried out by the reaction of Py-PDMS with methyl iodide. In order to evaluate the activity of MePy-PDMS as a transdermal penetration enhancer, the permeability of indomethacin through rabbit abdominal skin with and without MePy-PDMS was measured by in vitro experiment. MePy-PDMS showed effective enhancing activity for drug penetration through the skin. It was also revealed that the enhancing activity was due to an increase of the partition coefficient of the drug into the stratum corneum, from the determination of kinetic parameters in the drug permeation.