Rosmarinic acid (RA), an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid, is a potent radical scavenger, a chelator of prooxidant ions, and an inhibitor of lipid peroxidation. RA-containing extracts are widely used natural antioxidants in food products, and many herbal preparations and food supplements, containing RA, are marketed with claims of beneficial health effects. The current study investigated the effectiveness of subcritical water extraction (SWE) for the recovery of RA from lemon balm (Melissa officinalis), as a “green” alternative to conventional hydro-alcoholic extraction. Different durations (10 min and 20 min) and extraction temperatures (100 °C and 150 °C) were applied. Subcritical water applied at a temperature of 100 °C was equally efficient as 50% ethanol in extracting RA. However, the further elevation of temperature to 150 °C decreased RA content by up to 20% due to thermal degradation. The content of RA in dried extracts was between 2.36% and 5.55% and the higher temperature of SWE increased extract yield by up to 41%. The higher extraction yield resulted from the degradation of plant material by subcritical water as evidenced by the increased extraction and degradation of proteins, pectin, and cellulose. These results reveal that SWE is an efficient technology for the extraction of RA and other antioxidants from lemon balm at reduced extraction time and without the use of toxic organic solvents. Furthermore, by modification of SWE conditions, dry extracts with different purity and content of RA are obtained. These extracts could be used in the food industry as food antioxidants, or in the development of food supplements and functional foods.

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Overcoming solubility problems is the greatest challenge during formulation of poorly soluble active pharmaceutical ingredients (API’s) into oral solid dosage forms. Different formulation approaches were used to surpass this problem and enhance their solubility in the gastrointestinal (GI) fluids, in order to achieve a faster dissolution and better absorption, which will directly influence their therapeutic effect. In this paper, an evaluation of the potential of a self-emulsifying drug delivery system (SEDDS) to improve the solubility of the active ingredient cefuroxime axetil (CA) was done. Screening of the solubility of the API in different excipients was done, and Tween 80, PEG 400, and Olive oil as a surfactant, co-solvent, and oil, respectively, were chosen as the most convenient system constituents. An optimal self-emulsification and solubilization ability of this system was assessed using mixture experimental design statistical tools based on the response surface methodology (RSM). The prepared CA-SEDDS were evaluated for droplet size (d10, d50, d90 in µm), droplet size distribution (Span factor), and absorbance. As a complementary approach, for better representation of the non-linear relationship between the formulation compositions and the observed dispersion characteristics an artificial neural network (ANN) was used. Optimal formulation that consists of 10% (w/w) Tween 80 as surfactant, 80% (w/w) PEG 400 as co-solvent and 10% (w/w) Olive oil, was obtained. Both, mixture experimental design and ANN were combined for a comprehensive evaluation of CA-SEDDS and the obtained results suggested that formulation of SEDDS is a useful approach for improving the solubility of the CA. Keywords: self-emulsifying drug delivery systems (SEDDS), cefuroxime axetil, design of experiment, artificial neural network (ANN)