Contents lists available at ScienceDirect Chemical Engineering & Processing: Process Intensification journal homepage: www.elsevier.com/locate/cep PVP/flavonoid coprecipitation by supercritical antisolvent process Gulay Ozkan a , Paola Franco b , Esra Capanoglu a , Iolanda De Marco b, * a Department of Food Engineering, Faculty of Chemical and Metallurgical Engineering, Istanbul Technical University, 34469 Maslak, Istanbul, Turkey b Department of Industrial Engineering, University of Salerno, Via Giovanni Paolo II, 132, 84084, Fisciano SA, Italy ARTICLE INFO Keywords: Quercetin Rutin Polyphenols Polyvinylpyrrolidone Coprecipitated microparticles SAS process ABSTRACT To date, various delivery systems have been developed to improve chemical stability and increase the bioa- vailability of polyphenolic compounds. In the present study, the micronization of two flavonoids, quercetin and rutin, and their coprecipitation with polyvinylpyrrolidone (PVP) were studied using the supercritical antisolvent process (SAS). SAS process parameters were optimized with the aim of obtaining composite microspheres with controlled mean size and particle size distribution. Spherical microparticles (with mean diameters in the range between 0.47 and 9.52 μm for PVP/quercetin and in the range 0.84–8.17 μm for PVP/rutin) were precipitated, depending on the operating conditions. In correspondence of the best operating conditions, the entrapment efficiency in PVP, for both flavonoids, was 99.8% and the dissolution rate from the coprecipitated powders was 10 and 3.19 times faster compared to the dissolution rates of unprocessed flavonoids for quercetin and rutin, respectively. 1. Introduction Quercetin is a flavonoid compound, belonging to the class of fla- vonols [1]. A variety of foods and vegetables [2], particularly onions, peppers, cranberries, blueberries, apples, cherries and grapes are con- sidered to be rich sources of quercetin [3]. Dietary sources rich of quercetin are also flowers, tea, nuts, tomatoes, many seeds, barks, leaves as well as medicinal botanicals, including Ginkgo biloba, Hyper- icum perforatum, and Sambucus Canadensis [4,5]. In plants, quercetin (structural formula shown in Fig. 1a) is commonly found in the form of glycosides [6]; among them, rutin (Fig. 1b) is the most widespread glycoside form of quercetin [7]. The use of these compounds has been associated with a wide range of biological activities, including anti- oxidant, anti-inflammatory, anticancer, antiviral as well as to prevent cardiovascular, pancreas and liver diseases [8–10]. On the other hand, quercetin and rutin undergo many chemical changes during food pro- cessing and storage, due to the effects of oxygen, temperature, pH, etc. Besides, these flavonoids show a poor water solubility and, thus, a re- duced bioavailability [8]. Considering that they are very interesting in the pharmaceutical and nutraceutical fields because of their numerous benefits to human health, flavonoids are frequently taken as supplements, and functional foods. Therefore, in order to preserve their properties and improve their bioavailability, different delivery systems, based on the coprecipitation of flavonoids with a suitable polymer, have been developed [11]. Indeed, the active compound can be entrapped, impregnated in a polymer matrix, or encapsulated through a polymeric coating [12–14]. Some conventional micronization techniques, such as, for example, spray-drying, emulsification/solvent evaporation, centrifugal extrusion, freeze-drying and coacervation have been used to obtain coprecipitated particles [15]; however, using these processes, several limitations have been identified. Indeed, it is not easy to control the particle size dis- tribution, the product can be degraded because high temperatures and elevated quantities of residual solvent can cause the loss of its biological activity [16]. Techniques assisted by supercritical fluids, in particular supercritical carbon dioxide (scCO 2 ), can overcome these limitations [17,18]. Different processes have been proposed as an efficient alter- native to conventional ones for the micronization and coprecipitation of compounds belonging to different categories, such as products in agricultural, biomedical, pharmaceutical, food and cosmetic fields [19–21]. Supercritical carbon dioxide based techniques may be classi- fied according to the role played by the scCO 2 : indeed, it can play the role of solvent (like in the RESS, rapid expansion from supercritical solutions) [22], of antisolvent (like in the SAS, supercritical antisolvent process) [23], or of co-solvent (like in the SAA, supercritical assisted atomization process) [24]. In the SAS process, carbon dioxide is used as the antisolvent for the product to be micronized or coprecipitated [25,26]. Using the SAS technique, a wide variety of morphologies has been obtained, such as nanostructured filaments, nanoparticles with mean diameters in the range of 30–200 nm, spherical microparticles in https://doi.org/10.1016/j.cep.2019.107689 Received 2 September 2019; Received in revised form 4 October 2019; Accepted 17 October 2019 ⁎ Corresponding author. E-mail addresses: ozkangula@itu.edu.tr (G. Ozkan), pfranco@unisa.it (P. Franco), capanogl@itu.edu.tr (E. Capanoglu), idemarco@unisa.it (I. De Marco). Chemical Engineering & Processing: Process Intensification xxx (xxxx) xxxx 0255-2701/ © 2019 Elsevier B.V. All rights reserved. Please cite this article as: Gulay Ozkan, et al., Chemical Engineering & Processing: Process Intensification, https://doi.org/10.1016/j.cep.2019.107689