Effect of penetration enhancers on skin permeation of trazodone hydrochloride from matrix type transdermal formulation through mouse and human cadaver epidermis.
A transdermal dosage form of trazodone hydrochloride (TZN) may be useful in the treatment of moderate to severe depression in schizophrenic patients by providing prolonged duration of action. It will also improve patient compliance and bioavailability. Controlled input of TZN would attenuate fluctuating plasma level of TZN resulting from oral therapy. The aim of the current investigation was to evaluate its flux and the effects of various penetration enhancers, viz., isopropyl myristate (IPM), isopropyl palmitate (IPP), butanol and octanol on transdermal permeation from matrix-based formulations through the skin. The enhancing effect on the permeation of TZN was determined using the mouse and human cadaver epidermis. In vitro permeation data were collected at 37 degrees C using Keshary-Chien diffusion cells. The skin permeation was then evaluated by measuring the steady state permeation flux of TZN, enhancement ratio and the diffusion parameter. The highest enhancing effect was obtained with IPM followed by butanol, octanol and IPP. In general, higher fluxes were observed through mouse epidermis as compared with the human cadaver epidermis. The skin retention of TZN for both the species in the presence of different enhancers was nearly 3 times higher than for the control formulation. Based on the observed results, a transdermal patch of about 70 cm2 consisting of 10 % IPM should be able to attain and maintain therapeutic plasma concentration of TZN at 0.75 mg/mL over a period of 24 h.
Das
Malay K
MK
Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh-786004, India. du_mkd@yahoo.co.in
Bhattacharya
Asokangshu
A
Ghosal
Saroj K
SK
D020001:1-Butanol / Q000494:pharmacology; D020003:1-Octanol / Q000494:pharmacology; D000279:Administration, Cutaneous; D000328:Adult; D000818:Animals; D002626:Chemistry, Pharmaceutical; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009226:Myristates / Q000494:pharmacology; D010168:Palmitates / Q000494:pharmacology; D012869:Skin Absorption / Q000187:drug effects*; D014196:Trazodone / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D009226:Myristates; D010168:Palmitates; C008205:isopropyl myristate; C005060:isopropyl palmitate; D020001:1-Butanol; D020003:1-Octanol; D014196:Trazodone