ABSTRACT
Introduction .................................................................................................................................... 402 SEPA ................................................................................................................................................ 402 Scientific Rationale for Designing SEPA-Type Compounds.......................................................... 402 Experimental Data ...................................................................................................................... 403 Physical-Chemical Characteristics of SEPA................................................................................ 404 How Formulation Affects Skin Permeation Performance ......................................................... 405
Early Successes with SEPA ............................................................................................................. 406 Proof of Concept ........................................................................................................................ 406 In Vitro Absorption of Indomethacin .................................................................................... 406 In Vivo Percutaneous Absorption .......................................................................................... 406 Scalp Hair Growth in Balding Stumptail Macaque................................................................ 407
First Clinical Use of SEPA ........................................................................................................... 407 Nonclinical Evaluations of SEPA .................................................................................................... 409 Clinical Safety ................................................................................................................................. 412 Description of Selected Key Clinical Safety and Efficacy Studies............................................. 412
Clinical Programs............................................................................................................................ 412 Opterone1 .............................................................................................................................. 412 EcoNail ........................................................................................................................................ 414 Topiglan1 ............................................................................................................................... 414
Conclusions .................................................................................................................................... 414 References....................................................................................................................................... 415
Skin penetration enhancers have a long history of development, but none to date have been routinely incorporated into topical formulations. Limitations to their use have included incompatibility with the drugs they are coupled with and general safety or local irritation issues. Numerous compounds have been evaluated for skin penetration enhancing activity, including sulfoxides (such as dimethylsulfoxide, DMSO), Azone1
(e.g., laurocapram), pyrrolidones (for example, 2-pyrrolidone, 2P), alcohols and alkanols (ethanol and decanol), glycols (for example, propylene glycol, PG, a common excipient in topically applied dosage forms), surfactants (also common in dosage forms), and terpenes.
