Trazodone Hydrochloride (TZN), a serotonin uptake inhibitor, is used in the treatment of moderate to severe depression in schizophrenic patients. The undesirable side effects of TZN administered orally can be offset by using the transdermal route, which attenuates the fluctuating TZN levels (52 ââ?¬â?? 81 %) resulting from oral therapy. The present study is aimed for ex vivo and in vivo biopharmaceutical evaluation of transdermal matrix patch of TZN in rabbits. The TZN patch was prepared by solvent evaporation technique using Eudragit RL 100 and RS 100 polymers with triethylcitrate (plasticizer) and fennel oil (permeation enhancer). The ex vivo patch evaluation was performed using Keshary-Chien transdermal diffusion cell with mouse and human cadaver epidermis as membrane. TZN transdermal absorption from patch was compared to that from peroral TZN solution in rabbits. The steady-state skin permeation rate of 134.09 Ã?± 249 ?g/cm2/h and 135.75 Ã?± 1.18 ?g/cm2/h was achieved across mouse and human cadaver epidermis, respectively. The steady-state transdermal TZN concentration of 2.3 ?g/ml was achieved in rabbits after an initial lag time of ~ 2 h. the Cmax of peroral TZN solution was calculated to be 5.84 ?g/ml at a Tmax of 2 h indicating its rapid absorption compared to the transdermal administration with a Tmax of 5 h. The transdermal TZN bioavailability in rabbit is calculated to be 32 %. The ex vivo and in vivo biopharmaceutical parameters were in good agreement with respect to input rate, steady state plasma TZN concentration and lag time. The higher steady state blood concentration in rabbit than the effective blood concentration is expected to appear at 0.017 ?g/ml in human with a higher clearance value than that in rabbits. It can be estimated that a transdermal patch of about 40 cm2 containing 4 mg/cm2 of TZN is likely to be able to attain and maintain the therapeutic concentration (0.75 ?g/ml) of TZN over a period of 24 h and even further.
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