Abstract. Management of moderate or severe chronic pain conditions is the burden of clinicians dealing with patients trying to improve their quality of life and diminish their suffering. Although not a new opioid, tramadol has been recently rediscovered and widely used; this may be due to its favorable chronic safety and dependence profiles together with its high potency. Tramadol is a centrally acting analgesic with half-life of~6 h; therefore, it requires frequent dosing. It is freely soluble in water; hence, judicious selection of retarding formulations is necessary. The current study is focused on the innovation of a novel, simple, monolayer, easy-to-use, cost-effective, and aesthetically acceptable bioadhesive transdermal delivery system overcoming the defects of the conventional "patch" as carrier system for tramadol, ensuring its adequate delivery, along with the physicochemical evaluation of the designed formulations. Monolithic tramadol matrix films of chitosan, different types of Eudragit ® , and binary mixtures of both were prepared. As a single-polymer film, chitosan film showed best properties except for somewhat high moisture uptake capacity, insufficient strength and rapid release, and permeation. Polymer blends were monitored in order to optimize both properties and performance. Promising results were obtained, with chitosan-Eudragit ® NE30D (1:1) film showing the most desirable combined, sufficiently rapid as well as prolonged release and permeation profiles along with satisfactory organoleptic and physicochemical properties.

Abstract. This study is an extrapolation of our previous one (part I) concerned with the formulation and physicochemical evaluation of a novel, simple, monolayer, easy-to-use, cost-effective, and aesthetically acceptable bioadhesive transdermal patch for tramadol hydrochloride. The current work is focused on bioadhesion, skin tolerability, and pharmacodynamic evaluation. Using naked rat skin, chitosanEudragit® NE30D (1:1) film attained best bioadhesive properties. During in vivo studies, it also showed a significantly extended analgesic effect compared to both oral formula and chitosan single polymeric film using the hot plate test method. All the polymeric films were skin tolerable for the intended period of application according to the Draize test. The success of our approach can proudly, positively contribute into the world of pain management and arguably push transdermal delivery to realize its great promise.