Pharmacokinetics and Pharmacodynamics Evaluation of Tramadol in Thermoreversible Gels

Received Apr 11, 2017; Accepted Jun 20, 2017

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1. Introduction

Tramadol (TR) is an opioid analgesic widely used to treat moderate, severe, and chronic pain, such as oncologic and postoperatory pain [1, 2]. It acts as an opioid μ1 receptor agonist and monoamine reuptake inhibitor and as a target for some protein coupled receptor and ligand-gated ion channels [3, 4]. The common adverse effects of tramadol are somnolence, seizures, nausea, and vomiting [4]. TR usually evokes a low incidence of adverse effects when compared to classical opioids, such as morphine and fentanyl [5]. Despite these advantages, TR presents short duration of action and it is necessary to make repeated doses or continuous infusion for a prolonged analgesic action [6, 7].

In this context, our research group developed drug deliveries systems with TR and poloxamer (PL) thermoreversible hydrogels for future treatment of postoperatory pain [5]. Poloxamers are copolymers composed of basic units of ethylene oxides and propylene oxides. The different number of these basic units in PL allows the formation of micelles with a hydrophobic core surrounded by a hydrophilic corona. PL have the ability, in concentrated solutions, of forming gels close to corporal temperatures because when the temperature rises, propylene oxides units are dehydrated and aggregate (micellar core), while the hydrophilic ethylene oxides units (micellar corona) remain hydrated. Thus, in low temperatures the system remains as fluids and this property can be used for parenteral administration of drugs and in high temperatures (close to corporal) it remains as semisolids and allows drug delivery for long periods of time [8–10].

Physicochemical...