Preparation, Morphology and Properties of Quercetin-Loaded Micropaticulate Cellulose Derivatives Blends for Drug Delivery

Quercetin (Q, 3,5,7,3’,4’-pentahydroxyflavone), a common dietary component occurring in various edible plant and herbal medicines, has shown anti-oxidant and anti-inflammatory properties in numerous mammalian cell systems, in vitro as well in vivo. Although the variety of its biological effects, the Q bioavailability is an important unsolved problem. Q, in fact, is poorly soluble and is unstable in gastric conditions, even if it is well absorbed by the small intestine. In the attempt to ensure gastric protection and better deliver of this drug, in this study we prepared Q gastro-resistant microspheres by solvent evaporation method, using cellulose acetate phthalate (C-A-P), cellulose acetate propionate (CAP) or their blends in different ratios as coating polymers. The formulation and preparation conditions (stirring speed, polymer concentration, drug-to-polymer ratio, temperature) were optimized to obtain high encapsulation efficiency and production yield. The synthesized microspheres were submitted to several chemical-physical analyses (light scattering, fluorescence and scanning electron microscopy, X-ray diffractometry, calorimetry, infrared spectroscopy) in order to evaluate the effect of the matrices composition on the morphology and properties of the microparticulate systems. Moreover, the release properties were investigated performing in vitro dissolution studies. The analyses evidenced that the microspheres were free-flowing and spherical in shape, Q was microencapsulated in the amorphous state and the drug content was near to the theoretical one. In vitro dissolution studies, carried out using a pH change method, showed that all samples ehibit a fairly gastroresistance with a typical biphasic drug release trend, due to the pH dependent solubility of the enteric polymers used as matrices. However, the matrices composition strongly affect the amount of drug released at high pH values: in fact, the amount of Q released in simulated intestinal fluid is about complete (ca. 90%) in the case of C-A-P microspheres but proportionally decreases with the CAP percentage in the system