In vitro studies on transdermal permeation of butorphanol.
The influence of the donor vehicles pH and the addition of laurocapram or transkarbam 12 as permeation enhancers on the transdermal permeation of butorphanol through human skin were examined with the aim of finding out about its possible use in the transdermal delivery system. As the pH of the donor vehicles rises, the mean value of butorphanol skin fluxes declines; an exponential relationship of the means of butorphanol flux values against the pH of the buffered aqueous donor vehicles has been demonstrated. The presence of 1% of transkarbam 12 (T12) or 5% of laurocapram (LC), respectively, in an isopropylmyristate (IPM) donor vehicle increased transdermal fluxes of butorphanol almost 2.5 times (58.1+/-5.7 microg cm-2 hr-1) or 1.5 times (36.4+/-7.0 microg cm-2 hr-1), respectively, when compared to blank donors. Considering clinical and pharmacokinetic data on butorphanol, it is possible to expect that a transdermal preparation sized 20 cm2 and possessing flux values ranging between 5.1 and 15.3 microg cm-2 hr-1 should be sufficient to achieve effective butorphanol transdermal fluxes, namely using IPM donors containing T12. In conclusion, butorphanol is a suitable candidate for transdermal administration and T12 is a very a suitable enhancer for it.
Svozil
Michal
M
Faculty of Pharmacy in Hradec Králové, Charles University in Prague, and Tissue Bank, Faculty Hospital in Hradec Králové, Heyrovského, Czech Republic.
Dolezal
Pavel
P
Hrabálek
Alexander
A
Mericka
Pavel
P
D000279:Administration, Cutaneous; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001381:Azepines / Q000494:pharmacology; D002077:Butorphanol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002219:Carbamates / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D005079:Excipients / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009226:Myristates; D010539:Permeability; D014677:Pharmaceutical Vehicles; D012867:Skin; D012869:Skin Absorption; D012995:Solubility
D000701:Analgesics, Opioid; D001381:Azepines; D002219:Carbamates; D005079:Excipients; D009226:Myristates; D014677:Pharmaceutical Vehicles; C492029:transkarbam 12; C008205:isopropyl myristate; C035229:laurocapram; D002077:Butorphanol