Transdermal delivery from eutectic systems: enhanced permeation of a model drug, ibuprofen.
The formation of eutectic systems between ibuprofen (ibu) and seven terpene skin penetration enhancers was studied and, by using the eutectic systems as donors, the effects of melting point depression of the delivery system on transdermal delivery were investigated. A range of ibu:terpene binary mixtures were melted together, cooled, and recrystallised. Composition/melting point phase diagrams were determined by DSC and FT-IR analysis was used to investigated the nature of the interaction. Permeation of ibu across human epidermal membrane from the eutectic system was measured and compared to the flux from a saturated aqueous solution across skin and skin pretreated with the terpenes. The eutectic, i.e. minimum, melting points of these systems ranged from 32 degrees C for ibu:thymol 40:60 (% w/w) to -13 degrees C for ibu:1,8-cineole 40:60 (% w/w) compared to 76 degrees C for ibu alone. FT-IR studies indicated that only the terpenes which formed hydrogen bonds with ibu produced eutectic systems. Each set of ibu:terpene eutectic systems produced a significant (t-test, p = 0.05) increase in flux compared to a saturated aqueous solution applied to untreated and to terpene pretreated skin. For example, ibu:thymol 40:60 (% w/w) produced a flux of 150 micrograms/cm2/h, 5.9 times the flux from a saturated aqueous solution with thymol pretreated skin and 12.7 times the flux from a saturated aqueous solution across non-pretreated skin. In conclusion, a hydrogen bonding interaction is the primary mechanism by which some terpenes form binary eutectic mixtures with ibu. The resultant melting point depression of the delivery system is correlated with a significant increase in transdermal permeation.
Stott
P W
PW
Postgraduate Studies in Pharmaceutical Technology, School of Pharmacy, University of Bradford, UK.
Williams
A C
AC
Barry
B W
BW
D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002152:Calorimetry, Differential Scanning; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010539:Permeability; D012867:Skin / Q000378:metabolism*; D017550:Spectroscopy, Fourier Transform Infrared; D013729:Terpenes / Q000008:administration & dosage*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013729:Terpenes; D007052:Ibuprofen