Copaiba oil-resin (CO) is a naturally-occurring compound extracted from the trunks of Copaifera spp. trees, native to Latin America and West Africa [[1], [2], [3], [4], [5], [6]]. This compound has evolved as a protective mechanism for plants against various threats, including animals, fungi, and bacteria. CO is a viscous, generally yellow liquid composed of sesquiterpenes (volatile compounds) and diterpenes (resinous fraction) [7]. It has been approved as a flavoring agent by the Food and Drug Administration (FDA) since 1972 [8]. As a result of its composition, this oil exhibits several therapeutic properties, such as anti-inflammatory [9,10], wound healing [11], antibacterial [12,13], antitumoral [14], and antileishmanial [15] activities. Additionally, its oily nature makes it an effective emollient agent. Therefore, it is highly recommended for the treatment of skin wounds, wherein the ideal therapy must ensure maximum contact between the formulation and the targeted tissue. However, the direct application of the raw oil is not appropriate due to its slow and poor topical absorption [7,16], and its low viscosity, which tends to spread away from the application site [10,17]. These drawbacks conduce to a poor patient compliance to the therapy.

In this sense, the incorporation of CO into a controlled-release system can offer a promising alternative for the treatment of skin diseases, enabling improved delivery of therapeutic molecules to the target site. Furthermore, this strategy can promote these molecules easily permeate between cells and penetrate various layers of the skin, reaching the depth of the affected tissue.

An emulgel is a colloidal system resulting from the dispersion of an emulsion in a gel with the addition of a complex polymer [18]. The composition of this system impacts its properties [19,20]. Stimuli-responsive systems to external changes are particularly interesting since the injured area often exhibits distinct characteristics, such as an increased local temperature. Formulations containing poloxamer 407 (P407), referred to as thermoresponsive systems, respond to temperature variations by transitioning from a liquid to a gel state when it is present in adequate concentrations, above the critical micellar concentration (CMC). This reorganization into micelles minimizes the free energy of the solution [21,22], resulting in increased viscosity and gelation, promoting longer retention of the oil at the application site [[23], [24], [25], [26]]. P407, a non-ionic amphiphilic triblock copolymer and composed of poly (ethylene oxide)- poly (propylene oxide)- poly (ethylene oxide) (PEO-PPO-PEO) units, acts as an oil permeation enhancer by reducing the interfacial tension between oil and water. Studies conducted by Barbosa and colleagues (2017) showed that the P407 and Carbopol 974P® (C974P) combination constitutes polymeric blends that not only confers bioadhesive properties to the systems but also improves their rheological and mechanical characteristics [26].

Carbopol polymers were the first commercial carbomers created over 50 years ago and have been widely used as pharmaceutical excipients because of their versatility and high tolerability. They can modify formulation rheology, stabilize suspensions, promote the extended drug release, confer mucoadhesive properties, and enhance drug bioavailability [27,28]. When neutralized in aqueous solution, they can form gels [29]. Derived from polyacrylic acid and characterized by high molecular weight, the polymers of this group are very similar chemically, but vary in crosslinking density, viscosity profiles, polymerization solvents employed during synthesis, and flow characteristics [27]. Thus, the choice of carbomer type to compose the polymer network directly impacts the system's performance.

Our research group developed and evaluated systems consisting of Pluronic® F127 (trade name for P407) and Carbopol 934P® (C934P), aiming to establish a suitable pharmaceutical platform for the controlled release of Copaiba oil, for the treatment of cutaneous wounds [17,[30], [31], [32]]. C934P finds extensive application in pharmaceutical products owing to its high crosslinking degree, which forms viscous and stable gels characterized by bioadhesive properties. However, similar to other traditional carbomers, the use of benzene in C934P as the polymerization solvent is increasingly restricted by regulatory agencies due to residual traces in the molecule [27]. Therefore, it is important to consider the investigation of similar systems employing alternative bioadhesive carbomers that are more toxicologically preferable. C974P is highly cross-linked, yielding viscous and stable gels with viscoelastic fluid flow behavior. It is synthesized with ethyl acetate, making it a more suitable choice for the development of new medicines [28,33,34].

The strategy by combining CO, P407, and C974P can offer substantial advantages in terms of formulation's physicochemical stability, ease of administration and retention at the site of application, controlled drug release and improved permeation. However, the use of different types of carbomers can change the physicochemical properties and permeation performance of emulgel [17,20,28]. Therefore, the aim of this work was to develop and investigate the effect of C974P on rheological, mechanical, bioadhesive, in vitro drug release and ex vivo skin permeation properties of this system.