Polymeric percutaneous drug penetration enhancer - Synthesis and enhancing property of PEG/PDMS block copolymer with a cationic end group

Poly(ethylene glycol)/polydimethylsiloxane (PEG/PDMS) block copolymers containing an ammonium moiety at one chain end with various molecular weights were prepared to develop a silicone-based polymeric transdermal penetration enhancer. As the precursor of the desired block copolymer, 3-chloropropyl-terminated PEG/PDMS block copolymers were prepared via an initiator method, i.e. the anionic ring-opening polymerization of hexamethylcyclotrisiloxane was carried out by initiating with silanolate anion derived from PEG-silanol, alpha-3-(dimethylhydroxysilyl)propyl-omega-methyl-PEG oligomer. The initiator, PEG-silanol, was obtained from alpha-allyl-PEG by hydrosilylation with dimethylethoxysilane, followed by hydrolysis of the ethoxysilyl group. The enhancing activity in the drug penetration was evaluated by in vitro experiments using a two-chamber diffusion cell. Indomethacin and antipyrine were used as hydrophobic and hydrophilic model drugs, respectively, and the amounts of drugs permeating through the rabbit abdominal skin were measured with or without these polymeric enhancers. These enhancers were very effective for the penetration of hydrophilic drug, but not for that of hydrophobic one. On the other hand, the enhancing activities were influenced by the chain length of PDMS and PEG components. A suitable balance between the hydrophobic PDMS segment and the hydrophilic PEG segment would exist for a high enhancing activity of drug penetration. It was also found that the enhancing activity was due to an increase of the partition coefficient of a drug into the stratum corneum, from the determination of kinetic parameters in the drug permeation. (C) 1997 Elsevier Science B.V.