Available online at www.sciencedirect.com Chemical Engineering and Processing 47 (2008) 1594–1602 Precipitation of lutein and co-precipitation of lutein and poly-lactic acid with the supercritical anti-solvent process F. Miguel, A. Mart´ın ∗ , F. Mattea, M.J. Cocero High Pressure Processes Research Group, Department of Chemical Engineering and Environmental Technology, University of Valladolid, 47011 Valladolid, Spain Received 31 January 2007; received in revised form 24 July 2007; accepted 25 July 2007 Available online 31 July 2007 Abstract The supercritical anti-solvent (SAS) process has been used to re-crystallize lutein from ethyl acetate solutions. The influence of several process parameters (pressure, temperature, initial concentration, CO 2 and solution flowrates) on the particle size and morphology have been studied. The results have been compared to these obtained with other carotenoids (-carotene and lycopene) with similar operating conditions, and have been interpreted with the aid of a phase equilibrium model based on the perturbed hard sphere chain equation of state. Large differences in particle size have been observed between the experiments performed in the two-phase and the single-phase regions of the vapor–liquid phase diagram. A change in the particle morphology, from agglomerated microparticles to polygonal crystals, has been observed when the CO 2 /solution flow ratio was increased or the initial concentration was decreased. As a result of the precipitation, the purity of the lutein has been increased from 75% to over 90%. The co-precipitation of lutein with poly-lactic acid (PLA) has also been studied. A reduction in the particle size with the polymer/drug ratio has been observed, down to a minimum diameter of 1–5 m. © 2007 Elsevier B.V. All rights reserved. Keywords: Supercritical carbon dioxide; Carotenoid; Biopolymer; Re-crystallization; Perturbed hard sphere chain (PHSC) equation of state 1. Introduction The growing concern about the potential effect of synthetic food additives on human health is leading to the substitution of these additives by natural products. In this context, the use of carotenoids as natural colorants has an increasing industrial interest. Carotenoids are natural pigments responsible for the red, orange and yellow color of many vegetables and other ali- ments. Some of the most abundant carotenoids of the dozens present in the human organism are -carotene, lycopene, zeax- anthin and lutein (Fig. 1). These substances are not produced by the human body, and therefore they must be obtained from food. The most important sources of carotenoids in the human diet are green vegetables, tomatoes, carrots, citrics and eggs [1]. Since they are authorized food ingredients, carotenoids are widely used in the food, cosmetic and pharmaceutical industries as natural colorants or as antioxidants. ∗ Corresponding author. Tel.: +34 983 42 31 74; fax: +34 983 42 30 13. E-mail address: mamaan@iq.uva.es (A. Mart´ın). Besides their use as pigments, carotenoids have several phar- maceutical and nutritional applications due to their positive effect on health [2,3]. Due to these biological functions, lutein as well as other carotenoids, are frequently added to enriched ali- ments (milk, cereals, soups, etc.) and multivitamin complexes. The product supplied to these industries is usually presented as a mixture of the carotenoid and a biopolymer, since this formu- lation facilitates the handling of the product, and improves its stability [4]. Due to its antioxidant activity, it is not surprising that lutein becomes easily oxidized in the presence of oxygen, with light or at moderate temperatures [5]. Moreover, for its application in the food or pharmaceutical industries, an organic solvent-free product is needed. The supercritical anti-solvent (SAS) process is a very convenient alternative for meeting these requirements. If a suitable anti-solvent such as supercritical carbon dioxide (SC-CO 2 ) is used, it is possible to carry out the process at near ambient temperatures and in an inert atmosphere, thus avoid- ing the thermal degradation and the oxidation of the product. Due to the high solubility of organic solvents in SC-CO 2 , it is possible to obtain a solvent-free product without a complex 0255-2701/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.cep.2007.07.008