RESUMEN
ABSTRACT The aim of this paper was to study and optimize the dynamic maceration process to obtain Matricaria chamomilla L., Asteraceae, inflorescences extracts with optimum flavonoid content and antioxidant activity using a multivariate approach. Hydroalcoholic extracts were obtained by dynamic maceration in lab scale and the influence of extraction temperature, ratio of plant to solvent, ethanol strength; extraction time and stirring speed on the flavonoid content and antioxidant activity were unveiled using a fractional factorial design. The ethanol strength, ratio of plant to solvent and temperature were the three factors that influenced most the extract properties and were studied by a central composite design. Total flavonoid content and antioxidant activity were affected by the ethanol strength and ranged from 1.49 to 3.95% and 13.3 to 36.2 µg/ml, respectively. The desirability functions resulted in an optimal dynamic maceration condition using 1 h extraction at stirring speed of 900 rpm, ethanol 74.7%, temperature of 69 °C and using 36.8% of plant in solvent (w/v). Under this set of conditions, the extract had total flavonoid content of 4.11 ± 0.07%, in vitro antioxidant activity with IC50 of 18.19 µg/ml and apigenin and apigenin-7-glycoside contents of 2.0 ± 0.1 mg/g and 20.1 ± 0.9 mg/g, respectively. The results showed a low solvent consumption compared to previous works. The model was able to predict extract properties with maximum deviation of 12% and the extraction process developed herein showed to be reliable, efficient and scalable for M. chamomilla inflorescences, enriched with flavonoids, apigenin and apigenin-7-glycoside and high antioxidant activity.
RESUMEN
Solid dispersions have been successfully used to enhance the solubility of several poorly water soluble drugs. Solid dispersions are produced by melting hydrophilic carriers and mixing in the poorly water soluble drug. Supersaturation is obtained by quickly cooling the mixture until it solidifies, thereby entrapping the drug. The effects of using ultrasound to homogenize the molten carrier and drug mixture were studied. In particular, the increase in drug solubility for the resulting solid dispersions was analyzed. Piroxicam, which has very low water solubility, was used as a model drug. A full factorial design was used to analyze how sonication parameters affected the solubility and in vitro release of the drug. The results show that the use of ultrasound can significantly increase the solubility and dissolution rate of the piroxicam solid dispersion. Pure piroxicam presented a solubility of 13.3 µg/mL. A maximum fourfold increase in solubility, reaching 53.8 µg/mL, was observed for a solid dispersion sonicated at 19 kHz for 10 min and 475 W. The in vitro dissolution rate test showed the sonicated solid dispersion reached a maximum rate of 18%/min, a sixfold increase over the piroxicam rate of 2.9%/min. Further solid state characterization by thermal, X-ray diffraction and Fourier transform infrared analyses also showed that the sonication process, in the described conditions, did not adversely alter the drug or significantly change its polymorphic form. Ultrasound is therefore an interesting technique to homogenize drug/carrier mixtures with the objective of increasing the solubility of drugs with poor water solubility.