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The Effect of Chemical and Physical Enhancers on Trolamine Salicylate Permeation through Rat Skin Zadeh, Behzad Sharif Makhmal & Hasani, Mohammad Hossin Abstract Purpose: To achieve percutaneous delivery of trolamine salicylate to muscle and joints for the treatment of inflammatory muscle, tendon and joint diseases. Methods: Trolamine salicylate permeability parameters through rat skin were evaluated with and without chemical enhancers -Transcutol, eucalyptus oil, oleic acid and sodium lauryl sulfate –using the permeability cell technique. Results: The main barrier for trolamine salicylate permeability was the epidermis layer of the skin. Also, partitioning from the aqueous donor phase into the skin was the rate-limiting step for drug flux. Transcutol and eucalyptus oil were the most effective enhancers as they increased flux 11-fold. Sodium lauryl sulfate disrupted the lipid structure of the skin and thus increased diffusion coefficient 3-fold. Supersaturation technique did not increase flux. Propylene glycol in cosolvent system increased drug solubility in donor phase and partitioning. Conclusion: Trolamine salicylate exhibited less flux and diffusion coefficient through rat skin than salicylic acid due to its hydrophilic property. Partitioning from vehicle into skin was the rate-limiting step for trolamine salicylate permeability through rat skin. Keywords Trolamine salicylate, Percutaneous absorption, Chemical enhancers, Supersaturation technique, Differential scanning calorimetry

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