Particle design using supercritical CO2 has been of great interest in the pharmaceutical, microelectronic, catalytic, and related industries over the past 10 years. There have been numerous papers and patents published on the processes studied in this work. The solubility of most drug compounds in carbon dioxide is very low, making it a very attractive antisolvent for particle formation at suitable ranges of temperatures and pressures. This thesis explores the use of different CO2 antisolvent precipitation system designs for the formulation of small crystalline drug particles of a given size, morphology, and uniformity, using the precipitation of acetaminophen from ethanol as an example. In order to understand the precipitation process, the equilibrium concentration of acetaminophen in CO2 and CO2 plus ethanol were measured at a range of temperatures and pressures in a high-pressure extraction system. This information is important in understanding the supersaturation of the drug at various precipitation conditions. Several antisolvent processes were tested in order to determine their effectiveness in controlling the precipitation of acetaminophen from ethanol. The first system involved the use of Solvent Enhanced Dispersion by Supercritical Fluids (SEDS) patented by Hanna and York (WO9501221, 1994). This process uses a coaxial nozzle design where the solvent with the solute of interest is injected in the inner tube and the supercritical CO2 is injected in the outer tube. The two streams mix at nearly constant pressure and temperature in a small volume region of the nozzle before expanding through the nozzle tip into a chamber maintained at a fixed temperature and pressure. The fast mixing process rapidly expands the solvent with CO2 in order to induce phase split of the solid drug particles. The chamber pressure is maintained constant and nearly equal to the pressure in the nozzle. This process was studied because it was claimed that SEDS gave the best control of sy.

Keywords: acetaminophen, carbon dioxide, SEDS, PCA, supercritical, crystallization, formulation, particle design, drug, precipitation.

Particle formation with supercritical fluids is a promising alternative to conventional precipitation processes as it allows the reduction of particle size and control of morphology and particle size distribution without degradation or contamination of the product. The book comprehensively examines the current status of research and development and provides perspectives and insights on promising future directions.The introduction to high pressure and high temperature phase equilibria and nucleation phenomena provides the basic principles of the underlying physical and chemical phenomena, allowing the reader an understanding of the relationship between process conditions and particle characteristics.Bridging the gap between theory and application, the book imparts the scientific and engineering fundamentals for innovative particle formation processes. The interdisciplinary "modus operandi" will encourage cooperation between scientists and researchers from different but complementary disciplines. - Focuses on the general principles of particle formation in supercritical fluids - Considers high pressure and high temperature phase equilibria, fluid dynamics and nucleation theory - Discusses the underlying physical and chemical phenomena needed to understand the different applications, pointing out the relationship between process conditions and product properties

This book provides deep insights on the fundamentals, applications and perspectives of the Supercritical AntiSolvent (SAS) Precipitation Process. Chapter 1 provides recent (2013-2018) reports on the use of supercritical CO2 (SC-CO2) antisolvent for micronization, coprecipitation and fractionation of high-value products for the food, cosmetic and pharmaceutical industries. Chapter 2 discusses another variant of the SAS precipitation process called Supercritical fluid extraction of emulsions (SFEE). This chapter provides recent data from 2016-2018 reports investigation of supercritical extraction of emulsions (SFEE) to encapsulate compounds of great interest to the food and non-food industry. Chapter 3 details the design and construction of a SAS Precipitation equipment. Chapter 4 presents experimental results regarding the validation of the supercritical particle formation equipment. Chapter 5 shows the effects of process parameters during particle precipitation using Combined High Turbulence Extraction Assisted by Ultrasound and Supercritical Antisolvent Fractionation (SAF) processes applied to semi-defatted annatto seeds, as a model raw material plant, were investigated. Chapter 6 shows experimental results regarding the process Ultrasound Emulsification Assisted by Nitrogen Hydrostatic Pressure (UEANHP), during the emulsification preparation step of the Supercritical Fluid Extraction of Emulsions (SFEE) process, one of the options of the SAS Precipitation-based process. Finally, Chaptesr 7 and 8 present some perspectives about the economics and process integration with other processes aiming the development of novel conceptual biorefinering approaches for plant materials valorization.

This book presents the latest achievements of separation science and technology. It highlights the application of separation with regard to problems of current interest, such as the protection of the environment and the development of emerging technology, including chemical engineering, biotechnology, renewable energy sources and recycling of materials.

Clear evidence of increasing demands in the processing industry prompted the editors and authors to publish a new book about High Pressure Process Technology: Fundamentals and Applications.This book presents the latest knowledge regarding the high pressure processing aspects combined with that about the modeling, the design and the operation of safe and reliable high pressure plants and equipment. This treatment and selection of the subjects is stimulating and unique. Consisting of nine chapters, each subdivided into several sections, the book addresses the high pressure aspects, providing well selected correlated information connected with a comprehensive overview together with a large number of references. The main body of the first eight chapters refers to subjects like high pressure in general, the thermodynamics and kinetics of the fluids involved, the design of high pressure equipment, the modeling and design of reactors, separation and fractionation units, the safety aspects, the control and economics.In the extended last chapter, examples of promising high pressure applications are explained, such as chemical and enzymatic reactions in supercritical solvents, hydrogenation under supercritical conditions, supercritical water oxidation, polymerization with metallocene catalysts, supercritical extraction, fractionation and precipitation, supercritical pharma processing, ultra-high pressure sterilization and supercritical dry-cleaning.