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This work aimed at obtaining an optimized itraconazole (ITZ) solid oral formulation in terms of palatability and dissolution rate by combining different polymers using hot melt extrusion (HME), according to a simplex centroid mixture design. For this, the polymers Plasdone® (poly(1-vinylpyrrolidone-co-vinyl acetate) [PVP/VA]), Klucel® ELF (2-hydroxypropyl ether cellulose [HPC]), and Soluplus® (SOL, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol) were processed using a laboratory HME equipment operating without recirculation at constant temperature. Samples were characterized by physicochemical assays, as well as dissolution rate and palatability using an e-tongue. All materials became homogeneous and dense after HME processing. Thermal and structural analyses demonstrated drug amorphization, whereas IR spectroscopy evidenced drug stability and drug-excipient interactions in HME systems. Extrudates presented a significant increase in dissolution rate compared to ITZ raw material, mainly with formulations containing PVP/VA and HPC. A pronounced improvement in taste masking was also identified for HME systems, especially in those containing higher amounts of SOL and HPC. Data showed polymers act synergistically favoring formulation functional properties. Predicted best formulation should contain ITZ 25.0%, SOL 33.2%, HPC 28.9%, and PVP/VA 12.9% (w/w). Optimized response considering dissolution rate and palatability reinforces the benefit of polymer combinations.

Aedes aegypti is the main arbovirus vector transmitting chikungunya, Zika and dengue. The current vector control strategies are limited due to multiple insecticide resistance, deleterious impacts on the environment, and toxicity to non-target organisms. Bilobol, an alkylresorcinol isolated from the plant species Schinus terebinthifolia, demonstrated larvicidal activity against Aedes aegypti (LC50 7.67 mg/L in less than 24 h). To ensure that bilobol presents a viable alternative as an eco-friendly larvicide, this study aimed to explore the degradation process and acute toxicity of this alkylresorcinol in zebrafish, a non-target organism. A quantification method with validated parameters was developed and used to evaluate bilobol degradation in water over time. The Fish Embryo Toxicity (FET) test was applied to evaluate the acute toxicity of bilobol together with its degradation derivates. Results demonstrated that bilobol gradually degrades over time and almost completely disappears after 96 h, turning into small aliphatic chains which are less toxic than bilobol in its fundamental form. Therefore, it was possible to conclude that bilobol does not present significant toxicity to zebrafish embryos nor does it show signs of persistence in the environment. Additionally, bilobol can be found in high quantities not only in S. terebinthifolia, but also in cashew nut industry waste. Thus, bilobol constitutes an alternative environmentally friendly insecticide because it is not persistent, has indications of low toxicity to non-target organisms and presents a way to exploit massive quantities of material discarded by the food industry.