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Supercritical Antisolvent Micronization of Natural Carotene by the SEDS Process through Prefilming Atomization Wen Zhi He,*,†,‡ Quan Ling Suo,† Hai Long Hong,† Guang Ming Li,‡ Xiu Hua Zhao,‡ Chun Ping Li,† and Shan A† College of Chemical Engineering, Inner Mongolia UniVersity of Technology, Hohhot 010062, China, and School of EnVironmental Science and Engineering, Tongji UniVersity, Shanghai 200092, China
Natural carotene is micronized by the SEDS process through prefilming atomization (SEDS-PA) with the aim of evaluating the efficiency of prefilming atomization, examining the variation of carotene purity induced by the SEDS-PA process and studying the influence of operating variables on the particle size (PS) of the carotene precipitates. The carotene/dichloromethane solution to be atomized is driven through a liquid distributor with spiral slots in the prefilming atomizer as a thin film swirling at 45°. At the exit of the atomizer, the atomizing supercritical CO2 (SC-CO2) stream impinges on the film at 45°. Through the impingement and the use of swirling, the annular solution film is disintegrated into fine drops, and the mixing of the SC-CO2 and solution is intensified. Compared to the process in which solution is driven through the inner capillary of the atomizer while SC-CO2 is driven through its annular passage, the SEDS-PA process can obtain smaller droplets and finer microparticles with a narrower particle size distribution (PSD). After micronization by the SEDS-PA process, the purity of carotene microparticles is increased for unprocessed carotene with purity ranging from 30% to 87%, but it decreased for carotene with purity higher than 87%. The CO2 flow rate, solution flow rate, solution concentration, and pressure have marked influences on the particle size (PS), and the PSD broadens with increasing PS. Mechanisms that control PS are explained in terms of liquid atomization, agglomeration of particles, volumetric expansion of solution in SC-CO2, and nucleation and growth processes of particles. The dependence of the PS on temperature is not clear from all of the experiments performed. 1. Introduction Microparticle material formulations with a controlled particle size (PS) and particle size distribution (PSD) have many applications in the field of pharmaceutical drug delivery. Supercritical fluid precipitation (SFP) technologies1 that take advantage of the characteristics of supercritical fluids (SFs) to form microparticles have received increasing attention and been widely used to produce high-quality particulate pharmaceuticals. SFP technologies can precipitate micro- or even nanoparticles with narrow PSDs, reduce the residual solvent in the product to very low concentrations, and control product quality (PS, PSD, and particle morphology) in a wide range. Of the many possible SFs, carbon dioxide is the most widely used. It has a low critical point (Tc ) 304.1 K and Pc ) 7.38 MPa), and as a process solvent, it offers the additional benefits of being nontoxic, nonflammable, environmentally acceptable, and inexpensive. Moreover, the mild critical temperature makes it suitable for processing of thermally labile compounds. Rapid expansion of supercritical solutions (RESS), the first known SFP technology, consists of saturating supercritical CO2 (SC-CO2) with substrate(s) and then rapidly expanding the resulting solution into a low-pressure chamber through a nozzle to cause an extremely rapid nucleation of the substrate(s) in the form of monodisperse particles.2-4 RESS is a very attractive process, because it is simple and relatively easy to implement.1 The most important limitation of RESS precipitation is that most attractive substrates (polar or high-molecular-weight compounds) are not soluble enough in the SF to lead to profitable * To whom correspondence should be addressed. Tel.: +86-2165989215. Fax: +86-21-65989215. E-mail:
[email protected]. † Inner Mongolia University of Technology. ‡ Tongji University.
processes. A cosolvent can be used to improve this solubility, but it must be eliminated from the resulting powder, which is neither simple nor inexpensive. The gas (or supercritical fluid) antisolvent (GAS or SAS) process, in which SC-CO2 is used as an antisolvent for processing solids that are insoluble in SC-CO2, can be used to overcome the limitations of the RESS process.5 In the general GAS/SAS process, an organic solution of solute is atomized through a nozzle into a high-pressure vessel containing a nearcritical or supercritical fluid, causing intimate mixing of the solution and the fluid and resulting in liquid expansion and particle precipitation.6-8 The process of particles from gas-saturated solutions or suspensions (PGSS) consists of dissolving SC-CO2 into a liquid substance, a solution of the substance(s) in a solvent, or a suspension of the substance(s) in a solvent and then rapidly depressurizing this mixture through a nozzle, causing the formation of solid particles or liquid droplets depending on the system.9,10 Compared to RESS, this process can produce particles from a great variety of substances that need not be soluble in SC-CO2, especially with polymers that generally absorb a large concentration (10-40 wt %) of CO2 that either swells the polymer or melts it at a temperature much below (∼10-50 °C) its melting/glass transition temperature.1,11 The main limitation for the application of PGSS is solute thermal instability up to its liquefaction conditions. The prerequisites for a successful SAS/GAS precipitation are the complete miscibility of the liquid in SC-CO2 and the insolubility of the solute in it. For these reasons, SAS is not applicable to the precipitation of compounds dissolved in water because of the very low solubility of water in CO2 at the operating conditions commonly used. However, the limitation can be overcome by the atomization processes assisted by SCCO2.12-17 A first supercritical-fluid-based atomization method
10.1021/ie050993f CCC: $33.50 © 2006 American Chemical Society Published on Web 02/11/2006
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was proposed by Sievers and co-workers12-14 and called CANBD (carbon dioxide assisted nebulization with a bubble dryer). This technique is based on the mixing of SC-CO2 in a liquid solution and subsequent atomization of the formed mixture to generate a dense aerosol that is dried to form microparticles. In this process, with the scope of minimizing the time of contact between the liquid and SC-CO2, a low-dead-volume mixing tee (
