Ex vivo and in vivo evaluation of transdermal formulation of trazodone hydrochloride.
The aim of the present investigation is to evaluate the biopharmaceutical behaviors of the matrix patch containing trazodone hydrochloride (TZN) following transdermal administration in rabbits. The ex vivo skin permeation study was performed using Keshary-Chien glass diffusion cell and mouse epidermis with intact stratum corneum as membrane. The phosphate buffer of pH 7.4 was used as receptor solution at 37 degrees C. TZN patch was applied to the inner pinna skin of the rabbit. TZN transdermal absorption from patch was compared to that from peroral TZN solution in rabbit. A steady-state skin permeation rate of 134.09 +/- 2.49 microg/cm2/h was achieved from the matrix patch across mouse epidermis after an initial lag time of approximately 3.5 h. The steady-state transdermal TZN concentration of 2.3 microg/mL was achieved in rabbit from the matrix patch after an initial lag time of approximately 2 h. The Cmax of peroral TZN solution was calculated to be 5.84 microg/mL at a Tmax of 2 h indicating its rapid absorption compared to the transdermal administration with a Tmax of 5 h. The ex vivo and in vivo biopharmaceutical parameters were in good agreement with respect to steady-state plasma TZN concentration and lag time. The plasma level of TZN following transdermal application could be maintained for 24 h. The transdermal dose achieved a much higher steady-state blood concentration in rabbit compared with the effective blood concentration in human. The observed steady-state blood concentration may appear to be within the expected therapeutic range in human with a higher clearance value compared to that in rabbit.
Das
Malay K
MK
Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh 786004, Assam, India. du_mkd@yahoo.co.in
Ghosal
Saroj K
SK
D000279:Administration, Cutaneous; D000818:Animals; D002626:Chemistry, Pharmaceutical; D007408:Intestinal Absorption; D008297:Male; D051379:Mice; D011817:Rabbits; D012867:Skin / Q000378:metabolism*; D014196:Trazodone / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
D014196:Trazodone