Some species of Artemisia have traditionally been used as anthelmintics. The presence of toxic components in the extracts of these plants, such as αand β-thujones, and their poor aqueous solubility constitutes important limitations for their clinical applications. Recently, some thujones-free populations of A. absinthium have been cultivated in Zaragoza (Spain). The main aim of the present study was to design novel microemulsion (ME) formulations of thujones-free A. absinthium steam distilled extract (AAE) to improve its solubility and, subsequently, to enhance its oral bioavailability and nematocidal activity. A D-optimal mixture design was developed to optimize the ME system, based on droplet size distribution. The optimized formulation was analyzed for its conductivity and behavior in a gastric media and its nematocidal efficacy was evaluated in an ex vivo murine model for Trichinella spiralis larvae L1. The optimized ME was composed of Tween 80: propylene glycol (1.5:1) (66.45% w/w), AAE (29.35% w/w), and distilled water (4.25% w/w). It was seen that although the optimized ME has a W/O structure, it is capable of dispersing in the gastric environment in less than 15 minutes, forming 10 nm-sized droplets. A dilution of this ME, containing 0.05% w/w AAE, was prepared and its efficacy was compared with a 0.05% w/w AAE solution. The optimized ME decreased the intestinal parasites by up to 95.7%, while the solution of the extract showed a reduction of 86.5% (P = 0.0033). The results evidenced that the designed ME system provides a significant improvement of AAE in terms of aqueous solubility and nematocidal effect. It can also act as a promising formulation to improve the oral bioavailability of this hydrophobic extract, in order to design a future alternative to the classical treatments with benzimidazole drugs.
Background: Intestinal nematode infections are usually treated with benzimidazole drugs, but the emergence of resistance to these drugs has led to an increasing demand of new anthelmintic strategies. A new microemulsion formulation (ME) consisting of an Artemisia absinthium extract with proven nematocidal efficacy was previously developed. The aim of our study is to implement a D-optimal mixture design methodology to increase the amount of a silica material (loaded with this ME) in a tablet formulation, considering its tensile strength and disintegration time. Methods: 16 experiments or combinations of the 6 tablet components (loaded silica, microcrystalline cellulose, polyvinylpyrrolidone, croscarmellose, Syloid® 244 FP and magnesium stearate) were assessed. Tensile strength and disintegration time models were developed, and an optimization process was carried out. Results: Tensile strength was improved by increasing the polyvinylpyrrolidone content, while croscarmellose decreased the disintegration time. The optimized powder mixture contains 49.7% w/w of the loaded silica material. A compression force of 12 kN was applied to the powder mixture to form tablets with a tensile strength of 2.0 MPa and a disintegration time of 3.8 min. Conclusions: Our results show that D-optimal mixture designs provide a promising approach to formulate liquid-loaded silica materials.
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