Effect of Permeation Enhancers on the Release Behavior and Permeation Kinetics of Novel Tramadol Lotions

Purpose: The aim of this research work was to formulate, characterize and evaluate the in vitro permeation behavior of tramadol lotion containing propylene glycol (PG) and polyethylene glycol (PEG) as permeation enhancers. Methods: The permeation experiments were conducted in vitro using full thickness rabbit skin in Franz diffusion cells. The donor compartment was filled with PBS (phosphate buffered saline) at pH 7.4 ± 0.1. The receptor phase was continuously stirred PBS (pH 7.4) at 37 °C ± 0.5. The amount of tramadol permeated into the receptor phase was determined spectrophotometrically at 271 nm. Various permeation parameters such as permeation coefficient (Kp), diffusion coefficient (D), flux (J), input rate, and enhancement ratio were obtained using Fick’s diffusion laws. Results: Permeation increased with increase in the concentrations of both enhancers tested. Maximum cumulative amount permeated for control lotion (Lc) was 357 ìg/cm2/min with input rate 0.574 ìg/min and lag time (tlag) of 34.93 min, while for the optimum test lotion (L4, containing 8 % PG/PEG in ratio of 1:1 v/v), it was 926 ìg/cm2/min, 1.482 ìg/min and 58.36 min, respectively. The significantly (p < 0.05) higher permeability shown by the test lotion L4 can be attributed, in part, to the interaction of PG with intercellular lipids leading to the disruption of their organization and increasing their fluidity, and also partly as a result of solubilization of lipid bilayers by PEG. Conclusion: A binary system of PG and PEG in lotion can be successfully utilized for the permeation enhancement of tramadol. Keyword: Tramadol, Transdermal delivery, Permeation, Propylene glycol, Polyethylene glycol, Rabbit skin.