title: Percutaneous penetration enhancers in cigarette mainstream smoke.
abstract: Percutaneous penetration enhancers (PPEs) are chemicals used to enhance the transdermal delivery of drugs. Fifty-eight of the approximately 150 PPEs used for the transdermal delivery of drugs have been reported in cigarette mainstream smoke (MS). MS is a complex aerosol of minute liquid droplets (termed the particulate phase) suspended within a mixture of gases (CO(2), CO, NO(x), etc.) and semi-volatile compounds. The gases and many of the semi-volatiles are termed the vapor phase. Twenty-nine of the 58 PPEs have been identified in MS vapor phase, 15 in the particulate phase and 14 in both the vapor and particulate phases. There is a tendency for MS PPEs to be hydrophobic, with 40 of the 58 compounds (69%) being either hydrophobic or strongly hydrophobic, and only 24% being hydrophilic. Many of the 4800 known constituents of MS are hydrophilic and would not be expected to readily cross cell membranes or penetrate tissue when delivered as single compounds. The in vivo effect on biological activity of the juxtaposition within the cigarette smoke aerosol of the large number of hydrophilic constituents with the 58 PPEs is currently unknown. As an initial step in understanding this potential complex interaction, the 58 PPEs in MS have been identified and a number of molecular parameters related to the ability to penetrate tissue have been calculated, including MS concentration, measured and calculated base ten logarithm of the octanol-water partition coefficient (Mlog P and Clog P), molecular volume (MgVol) and calculated molar refractivity (CMR).
authors: R&D, Research and Development, RJ Reynolds Tobacco Company, Bowman Gray Technical Center, RJRT Company, Winston-Salem, NC 27102-1487, USA. smithc4@rjrt.com
authors: Carr J
authors: CJ
authors: Smith
authors: Thomas A
authors: TA
authors: Perfetti
authors: Rajni
authors: R
authors: Garg
authors: Patricia
authors: P
authors: Martin
authors: Corwin
authors: C
authors: Hansch
mesh_terms: D000279:Administration, Cutaneous; D000465:Algorithms; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D005079:Excipients / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D012869:Skin Absorption; D012906:Smoke / Q000032:analysis*; D014026:Nicotiana / Q000737:chemistry*
chemical_list: D005079:Excipients; D012906:Smoke