title: Effect of drug chirality on the skin permeability of ibuprofen.
abstract: The in vitro passive diffusion of S-ibuprofen (S-IB) and RS-ibuprofen (RS-IB) through human epidermis was determined to study the effects of drug chirality. S-IB has a lower melting point (T(m)=54 degrees C) than RS-IB (T(m)=77 degrees C) and, therefore, a greater solubility (S-IB: 127+/-1 microg/mL; RS-IB: 81+/-1 microg/mL). Supersaturated plasters were prepared by using a poly(dimethylsiloxane) adhesive and Eugragit RL and propylene glycol as antinucleant agents. The in vitro skin permeation profiles were determined by Franz cells and human epidermis obtained from three different donors. The permeation profiles of S-IB from saturated solutions resulted statistically higher than those of RS-IB (p<0.002). When plasters were used, no differences were noticeable between the enantiomer and racemate (p>0.17). The latter unexpected results could be explained considering that the RS-IB or S-IB in vitro release rate constants, determined using 3% w/w or 6% w/w loaded plasters, were not statistically different, suggesting that the drug diffusivity within the adhesive matrix represented the rate limiting step to the skin absorption.
authors.affiliation: Department of Pharmaceutical Sciences Pietro Pratesi, Università degli Studi di Milano, Milan, Italy. francesco.cilurzo@unimi.it
authors.forename: F
authors.initials: F
authors.lastname: Cilurzo
authors.forename: E
authors.initials: E
authors.lastname: Alberti
authors.forename: P
authors.initials: P
authors.lastname: Minghetti
authors.forename: C G M
authors.initials: CG
authors.lastname: Gennari
authors.forename: A
authors.initials: A
authors.lastname: Casiraghi
authors.forename: L
authors.initials: L
authors.lastname: Montanari
mesh_terms: D000279:Administration, Cutaneous; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D004058:Diffusion; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D004304:Dosage Forms; D004339:Drug Compounding; D004817:Epidermis / Q000378:metabolism*; D005079:Excipients / Q000737:chemistry; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008954:Models, Biological; D011108:Polymers / Q000737:chemistry; D019946:Propylene Glycol / Q000737:chemistry; D012869:Skin Absorption; D012995:Solubility; D013237:Stereoisomerism; D013678:Technology, Pharmaceutical / Q000379:methods; D014014:Tissue Adhesives / Q000737:chemistry; D044366:Transition Temperature
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004129:Dimethylpolysiloxanes; D004304:Dosage Forms; D005079:Excipients; D011108:Polymers; D014014:Tissue Adhesives; C058665:Eudragit RL; C013830:baysilon; D019946:Propylene Glycol; D007052:Ibuprofen