Folic acid–PVP nanostructured composite microparticles by supercritical antisolvent precipitation Valentina Prosapio, Iolanda De Marco ⇑ , Mariarosa Scognamiglio, Ernesto Reverchon Department of Industrial Engineering, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano (SA), ITALY highlights  Coprecipitation of spherical PVP + folic acid microparticles was obtained using SAS.  Nanoparticles (down to 50 nm), sub-microparticles (0.29–0.65 lm) and microparticles (0.8–3.8 lm) were obtained.  Crystallinity, drug effective loading, drug release profiles and FA degradation were measured.  Folic acid dissolution rate was significantly increased in the coprecipitated powders. article info Article history: Received 10 March 2015 Received in revised form 13 April 2015 Accepted 29 April 2015 Available online 5 May 2015 Keywords: Nanocomposites Microparticles Folic acid Polyvinylpyrrolidone Supercritical antisolvent process Precipitation mechanisms abstract In this work, supercritical antisolvent (SAS) precipitation was proposed for the production of polyvinylpyrrolidone (PVP)–folic acid (FA) microspheres, to test the applicability of this technique to the production of coprecipitates of biomedical interest with improved bioavailability. The effect of SAS operating parameters, such as polymer/drug ratio, pressure, temperature and concentration was investi- gated to identify successful process conditions. We obtained different kind of precipitates: nanoparticles with a mean diameter down to 50 nm, sub-microparticles with a mean diameter in the range 0.29– 0.65 lm and microparticles in the range 0.8–3.8 lm. These powders were characterized to determine drug effective loading and drug release profiles and to measure FA degradation. These analyses revealed that SAS process allowed the production of PVP–FA coprecipitates only in specific ranges of SAS process parameters and in the case of microparticles production. The drug dissolution rate of the PVP + FA copre- cipitates in a phosphate buffered saline solution (PBS) was about 20 times faster than the one of unpro- cessed FA. Moreover, SAS process had no significant detrimental effect on the stability of the vitamin. We tried to explain the precipitation mechanisms producing the observed morphologies and the large improvement of the FA dissolution rate, when it was encapsulated in PVP microparticles. Ó 2015 Elsevier B.V. All rights reserved. 1. Introduction Coprecipitated microparticles play an important role in various industrial fields, such as agriculture, biomedicals, pharmaceuticals, foods and cosmetics. Indeed, they can be used to protect the encap- sulated material against oxidation and deactivation, to achieve a controlled delivery of the active ingredients and to mask organoleptic properties like color, taste, and odor of the active compounds [1]. Folic acid (FA) or folates, belonging to vitamin B family, are rel- evant for the proper working of a variety of human physiological processes, such as biosynthesis of nucleotides, cell division, gene expression; moreover, FA is important in the prevention of neural tube defects in infants, vascular diseases and megaloblastic anemia [2]. However, FA is not produced by human body; therefore, it must be necessarily taken with the diet; but, natural folates in foods undergo degradation reactions when they are exposed to light, moisture, acid or alkaline medium, oxygen and high temper- atures [3]. A possible solution to improve folates stability and their bioactivity is represented by their coprecipitation with a biodegradable polymeric carrier that can protect the vitamin from degradation [4]. Moreover, since FA shows a low water solubility (0.0016 mg/mL), it is necessary to use a hydrophilic polymer to improve its bioavailability. Polyvinylpyrrolidone (PVP) is a water-soluble synthetic poly- mer, widely used as carrier in controlled release systems [5] or to enhance the dissolution rate of poorly water-soluble drugs [6]. Particularly, its ability to retard crystal growth makes it suitable for the coprecipitation with crystalline substances [5]. Since it http://dx.doi.org/10.1016/j.cej.2015.04.149 1385-8947/Ó 2015 Elsevier B.V. All rights reserved. ⇑ Corresponding author. Fax: +39 89 964057. E-mail address: idemarco@unisa.it (I. De Marco). Chemical Engineering Journal 277 (2015) 286–294 Contents lists available at ScienceDirect Chemical Engineering Journal journal homepage: www.elsevier.com/locate/cej