Encapsulation and Controlled Release Technologies in Food Systems

The emergence of the discipline of encapsulation and controlled release has had a great impact on the food and dietary supplements sectors; principally around fortifying food systems with nutrients and health-promoting ingredients. The successful incorporation of these actives in food formulations depends on preserving their stability and bioavailability as well as masking undesirable flavors throughout processing, shelf life and consumption.

This second edition of Encapsulation and Controlled Release Technologies in Food Systems serves as an improvement and a complement companion to the first. However, it differentiates itself in two main aspects. Firstly, it introduces the reader to novel encapsulation and controlled release technologies which have not yet been addressed by any existing book on this matter, and secondly, it offers an in-depth discussion on the impact of encapsulation and controlled release technologies on the bioavailability of health ingredients and other actives. In common with the first edition the book includes chapters written by distinguished authors and researchers in their respective areas of specialization.

This book is designed as a reference for scientists and formulators in the food, nutraceuticals and consumer products industries who are looking to formulate new or existing products using microencapsulated ingredients. It is also a post-graduate text designed to provide students with an introduction to encapsulation and controlled release along with detailed coverage of various encapsulation technologies and their adaptability to specific applications.

• Language: English
• Publisher: Wiley
• Release date: Mar 9, 2016
• ISBN: 9781118946879

Book preview

List of contributors

Ingrid, A.M. Appleqvist

CSIRO, Sydney, Australia

Abraham Aserin

Casali Institute of Applied Chemistry, The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel

Philip C.B. Christophersen

Department of Pharmacy, Faculty of Health and Medicinal Sciences, University of Copenhagen, Denmark

María José Cocero

Department of Chemical Engineering and Environmental Technology, University of Valladolid (Spain), Valladolid, Spain

Nissim Garti

Casali Institute of Applied Chemistry, The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel, Nutralease Ltd, Mishor Adumim, Israel

Gildas K. Gbassi

Université Felix Houphouët Boigny, Département of de Chimie Analytique, Chimie Générale et Minérale, Abidjan, Cote d'Ivoire

Matt Golding

Massey University, Palmerston North, New Zealand

Nicolaas Jan Zuidam

Unilever Food and Health Research Institute, Unilever R&D Vlaardingen, The Netherlands

Tansel Kemerli

Department of Chemical Engineering, Section of Food Technology, Gebze Institute of Technology, Turkey

Jamileh M. Lakkis

Expert in encapsulation and controlled release technologies, Barcelona, Spain

Xiang Li

Université de Strasbourg, Faculté de pharmacie, Laboratoire de Conception et d'Application de Molécules Bioactives, Illkirch Cedex, France

Ángel Martín

Department of Chemical Engineering and Environmental Technology, University of Valladolid, Valladolid, Spain

Diego Moretti

ETH Zürich, Department of Health Sciences and Technology, Institute of Food Nutrition and Health, aboratory of Human Nutrition Schmelzbergstrasse, Zürich, Switzerland

Huiling Mu

Department of Pharmacy, Faculty of Health and Medicinal Sciences, University of Copenhagen, Denmark

Trinh Lan Nguyen

Université de Strasbourg, Faculté de pharmacie, Laboratoire de Conception et d'Application de Molécules Bioactives, Illkirch Cedex, France

Murat Ozdemir

Department of Chemical Engineering, Section of Food Technology, Gebze Institute of Technology, Turdey

Samantha C. Pinho

Department of Food Engineering, School of Animal Science and Food Engineering (FZEA), University of São Paulo, Brazil

Eli Pinthus

Nutralease Ltd, Mishor Adumim, Israel, Adumim Food Ingredients, Mishor Adumim, Israel

Aviram Spernath

Casali Institute of Applied Chemistry, The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel

Curt Thies

Thies Technologies, Henderson, Nevada

Taise Toniazzo

Department of Food Engineering, School of Animal Science and Food Engineering, University of São Paulo, Brazil

Thierry F. Vandamme

Université de Strasbourg, Faculté de pharmacie, Laboratoire de Conception et d'Application de Molécules Bioactives, Illkirch Cedex, France

Salima Varona

Department of Chemical Engineering and Environmental Technology, University of Valladolid, Valladolid, Spain

Rob Vreeker

Unilever Food and Health Research Institute, Unilever R&D Vlaardingen, The Netherland

Mingshi Yang

Department of Pharmacy, Faculty of Health and Medicinal Sciences, University of Copenhagen, Denmark

Michael Zimmermann

ETH Zürich, Department of Health Sciences and Technology, Institute of Food Nutrition and Health, Zürich, Switzerland

Foreword

The biggest threat to the wider utilization of encapsulated ingredients in food formulations is the use of MIRAGE ENCAPSULATION. This unfortunate practice used by a few marginal suppliers, who resort to dry blending actives with excipients and label them as encapsulated ingredients, results in low-quality products which cast doubts on the benefits of true encapsulation.

Preface to second edition

The emergence of the discipline of encapsulation and controlled release has undoubtedly had a great impact on the food and dietary supplements sectors. However, a large gap still exists between the theoretical aspects of encapsulation and controlled release technologies and their potential applications.

This book edition represents a continued effort to bridge this gap. It is designed as an improvement and a complement to the first edition which was published in 2007. This edition differentiates itself in two main aspects. First, it introduces the reader to novel encapsulation and controlled release technologies which have not yet been addressed by any existing book on this matter, and second, it incorporates an elaborate discussion on the impact of encapsulation and controlled release technologies on the bioavailability of a select group of health ingredients. Similar to the first edition, this book includes chapters written by distinguished authors and researchers in their respective areas of specialization.

Chapters in this edition, except for two of them, are either entirely new or have been appropriately expanded:

Chapter 1 provides a general introduction to microencapsulation and controlled release technologies, mainly those adaptable to food applications. It also discusses briefly the concept of release kinetics and modes of release.

Chapter 2 authored by Dr. Cocero and co-workers discusses a novel approach to microencapsulation using supercritical fluid (SCF) technology. The chapter provides an elaborate discussion on particle formation processes using CO2-SCFs along with a case study highlighting the benefits and challenges of microencapsulating essential oils using such novel technologies.

Chapter 3 by Dr. Curt Thies presents an expanded version of the original chapter on encapsulation via complex coacervation. It provides a critical assessment of formulations on yield and stability of encapsulated food grade oils (orange, omega-3 fatty acids).

Chapter 4 by Dr. Pinho and Dr. Toniazzo introduces the reader to a new approach to microencapsulation via dried liposomes. The authors also discuss the potential of dried liposome microcapsules as a safer alternative to wet systems, especially for food applications.

Chapter 5 by Dr. Thierry Vandamme and his collaborators presents an overview of the role of excipients and encapsulating agents in preserving the stability and viability of encapsulated probiotic bacteria.

Chapters 6 by Dr. Klaas Jan Zuidam et al. dealing with emulsions as delivery systems and Chapter 7 by Professor Garti et al. on Nanosized Self-Assembled Liquid Vehicles have not been updated but are included in this edition due to the importance of the subject matters to the concepts of microencapsulation and controlled release.

Chapter 8written by the editor of this book (Dr. Lakkis) on encapsulation and controlled release applications in bakery products has been updated to include broader discussions and additional illustrations.

Chapter 9 also authored by the book editor has been rewritten to highlight novel approaches for delivering flavors, health as well as oral care actives via confectionery products.

Chapter 10 is written by two leading experts on bioavailability of minerals, Dr. Diego Moretti and Dr. Michael Zimmermann. This chapter presents an in-depth discussion on methods for assessing bioavailability and nutritional value of microencapsulated minerals.

Chapter 11 by Dr. Mu and collaborators presents a critical overview of current advances in assessing the impact of microencapsulation techniques on stabilizing omega-3 fatty acids and preserving their bioavailability.

Chapter 12 by Dr. Murat Ozdemir and Dr. Tansel Kemerli includes an expanded update on novel technologies for controlling the release of scents and fragrances, pigments, inks and time-temperature indicators in food packaging applications.

It is my hope that this new edition proves itself to be a useful source of information on microencapsulation and controlled release technologies, mainly for those involved in using them in the development of new products. A special effort was made to keep the text accurate, clear, and easy-to-read.

This new edition would not have been possible without the commitment and cooperation of the contributing authors who I am deeply indebted to. Thank you.

I also would like to acknowledge David McDade (excutive editor), Audrie Tan (project manager), and Anupama Kumari (project manager) and the editorial staff at Wiley-Blackwell, and also Jo Egré (freelance copy editor) for their continued support, advice, and patience throughout this project

As always I am very grateful for the readers of the first edition and welcome their continued feedback on this book.

Jamileh M. Lakkis

Preface to first edition

Encapsulation and controlled release technologies have enjoyed their fastest growth in the last two decades. These advances, pioneered by pharmaceutical companies, were a result of: (1) the rapid change in drug development strategies to target specific organs or even cells, (2) physicians' growing concern about patient non-compliance, and (3) pharmaceutical companies desire to extend their market monopoly on new drugs for a certain period of time, as provided by the US and international patent laws.

Despite this progress, encapsulation and controlled release technologies have only been recently adopted by the food industry. Food researchers and technologists have often been confronted with the dilemma of how to translate all these advances from the drug arena into practical applications in food systems. By searching the literature, one can find volumes of books and specialized publications on encapsulation and controlled release technologies. Unfortunately, most of these publications have dealt with theoretical aspects of these technologies, with little emphasis on real applications in consumer and food products.

This book attempts to illustrate various aspects of encapsulation and controlled release applications in food systems using practical examples. These examples will give the reader an appreciation for the delicate art of designing encapsulated ingredients and the enormous challenges in incorporating them into food formulations. Most of the practical examples in this book were borrowed from the patent literature. This approach might be questioned based on the fact that patents applications are never peer reviewed, but seems justifiable considering the frantic effort by both industry and academia to protect their discoveries and to gain limited-time monopoly on their innovations, thus limiting the availability of such information in peer-reviewed articles.

This publication has several potential uses. It is a reference book for scientists in the food, nutraceuticals, and consumer products industries who are looking to introduce microencapsulated ingredients into new or existing formulations. It is also a post-graduate text designed to give students some comprehension of various aspects of encapsulation and controlled release in food systems.

This book is organized in such a way that each chapter treats one major application of encapsulation and controlled release technologies in foods.

Chapter 1 introduces the readers to various encapsulation and controlled release technologies, as well as release mechanisms, suitable for applications in foods, nutraceuticals, and consumer products.

Chapter 2 by Professor Nissim Garti and his collaborators discusses a novel approach to encapsulation and controlled release via reverse microemulsion technique referred to as nanosized self-assembled liquids (NSSL). Such systems are shown to provide exceptional thermodynamic stability in a wide pH range. In addition to enhancing bioavailability of functional active ingredients, NSSL systems, by virtue of their unique transparent appearance, are excellent candidates for beverage applications.

Chapter 3, by Dr. Klaas-Jan Zuidam and co-workers, presents an elaborate approach to understanding emulsions and their benefits as delivery systems in food applications. This chapter discusses various mechanisms of emulsion stabilization and destabilization and how they can best be designed for targeted delivery of flavors and functional ingredients in the human gastrointestinal system.

Chapter 4 on encapsulation and controlled release of probiotics by Drs. Chen and Chen reports on approaches for encapsulating probiotic bacteria in dairy products as well as in the human gastrointestinal tract. This chapter also discusses novel optimization techniques for stabilizing these beneficial bacteria and enhancing their survival rates.

Chapter 5, written by the editor of this book, highlights current approaches to encapsulation and controlled release technologies for bakery products applications. Current encapsulation practices such as hot-melt particle coating and spray chilling are discussed. Examples of the performance of encapsulated leavening agents as well as sweeteners and flavors are presented in shelf-stable bakery applications.

Chapter 6 on nanoencapsulation technology by Dr. Huang and his collaborators deals with novel approaches to encapsulate enzymes and nutraceuticals. Specific examples are presented on stabilization of phytochemicals and their enhanced bioavailability via incorporation into nanoemulsions and bioconjugation systems.

Chapter 7 on flavor encapsulation via complex coacervation is written by Dr. Curt Thies. Discussion is focused on the basic principle of complex coacervation technique as a liquid–liquid polymer phase separation phenomenon. Guidance on polymer selection and subsequent implications on the physicochemical properties of capsules as well as their release behavior is provided.

Chapter 8, written by the editor of this book, details techniques used for delivering therapeutic as well as functional actives and flavors via confectionery products. Technologies and subsequent applications discussed in this chapter have wide applications in food and nutraceuticals, as well as in pharmaceutical arenas. Mechanisms and challenges specific to targeted release in upper gastrointestinal tract, especially the mouth and throat areas, will be described in great detail.

Chapter 9 discusses encapsulation and controlled release of actives in packaging applications by Dr. Ozdemir and collaborator. In this contribution, the authors provide examples on embedding fragrances, pigments as well as antimicrobial and insect repellent agents into food packaging films.

Chapter 10, authored by Ms. Kathy Brownlie, provides a marketing perspective of microencapsulation technologies and their potential impact on the food industry. Ms. Brownlie offers an in-depth assessment of market drivers as well as constraints that are still hindering wider implementation of these technologies in food manufacturing.

This book has definitely surpassed my vision and expectations thanks to the contributors and I am grateful to all of them for their expertise, commitment, and dedication. It is my hope that this book will prove itself a useful source on encapsulation and controlled release in a wide range of food and consumer product applications.

Many thanks to the editorial staff at Blackwell Publishing Co., especially to Mark Barrett and Susan Engelken, for their valuable help and advice throughout this project.

Last but not least, I would like to thank my parents who taught me the importance of working hard, having clear goals, and standing for what I believe is right. It is a lesson that guides me in everything I do.

Jamileh M. Lakkis

Chapter 1

Introduction

Jamileh M. Lakkis

Encapsulation and controlled-release systems are designed to protect actives from undergoing undesirable interactions while enhancing their functionality and bioavailability. Other objectives include masking the taste of bitter components, ensuring adequate administration of heat- or oxidation-labile health actives, and ensuring their delivery at a predetermined rate to a target site. In foods and nutraceuticals, encapsulation and controlled release have found applications in many categories such as confections, bakery, breakfast cereals, dairy products, beverages, packaging, among others. Markets and Markets Research estimated the value of food-related encapsulation market to reach $39.5 billion by 2020 (http://www.marketsandmarkets.com).

European Directive 3AQ19a defined controlled release as a modification of the rate or place at which an active substance is released. Such modification can be made using materials with specific barrier properties for manipulating the release of the active and to provide unique sensory and/or functional benefits.

The addition of small amounts of nutrients to a food system may not affect its appearance and taste significantly; however, incorporating high levels of nutrients to meet certain requirements or treat an ailment will most often result in unstable and unpalatable foods. Examples of such nutrients include fortification with calcium, vitamins, or polyunsaturated fatty acids, which often results in undesirable sensory changes such as grittiness, medicinal or oxidized taste, and others. Different types of encapsulation and controlled-release systems are currently available to help overcome these challenges and to provide a wide range of release requirements.

A wide variety of cores (encapsulants), wall-forming materials (encapsulating agents), and technologies are commercially available for manufacturing microcapsules and microparticles of different sizes, shapes, morphological properties, and costs, as well as controlling the release of the encapsulated actives.

Wall-forming materials

Materials used in microencapsulation as film coating or matrix-forming components include several categories:

Lipids and waxes: beeswax, candelilla and carnauba waxes, wax microemulsions and macroemulsions, glycerol distearate, and natural and modified fats

Proteins: gelatins, whey proteins, zein, soy proteins, caseins and caseinates, gluten, etc. All these proteins are available in both native and modified forms.

Carbohydrates: starches, maltodextrins, chitosan, sucrose, glucose, ethylcellulose, cellulose acetate, alginates, carrageenans, chitosan, etc.

Food-grade polymers: polypropylene, polyvinylacetate, polystyrene, polybutadiene, etc.

Core materials

These materials include flavors, antimicrobial agents, vitamins, minerals, antioxidants, probiotics, colors, acidulants, alkalis, buffers, sweeteners, enzymes, cross-linking agents, yeasts and chemical leavening agents, omega-3 fatty acids, and other nutrients.

Release triggers

Encapsulation and controlled-release systems can be designed to respond to one or a combination of triggers that can activate the release of the entrapped substance and to meet a desired release target or rate. Triggers can be one or a combination of the following:

Temperature: ideally for release of actives from fat/wax matrices, gelatin, and other meltable polymers

Moisture: essential for releasing actives entrapped in hydrophilic matrices

pH: can release actives from enteric-coated particulates or emulsions (coalescence)

Enzymes: can release actives from enteric-coated particulates due to disintegration of the wall material with amylases, proteases, lipases, etc.

Shear: chewing, physical fracture, and grinding represent physical means for release of actives during actual consumption

Lower critical solution temperature: release takes place at a critical temperature below which the components of a mixture are miscible for all compositions (often encountered in phase diagrams).

Payload

Payload is a term used to estimate the amount of active (core) entrapped in a given matrix or wall material (shell) and is expressed as:

equation

Current approaches to encapsulation and controlled release

Entrapment in carbohydrate matrices

Encapsulation into a carbohydrate matrix generally involves melting a crystalline polymer using heat and/or shear to transform the molecular structure into an amorphous phase. The encapsulant is then incorporated into the meta-stable amorphous phase followed by cooling to solidify the structure and form glass, thus restricting molecular movements.

Carbohydrates are excellent candidates for this type of encapsulation due to several attributes; they (1) form an integral part of many food systems, (2) are cost-effective, (3) occur in a wide range of polymer sizes, and (4) have desirable physicochemical properties such as solubility, melting, phase change, etc.

Sucrose, maltodextrins, native and modified starches, polysaccharides, and gums have been used for encapsulating flavors, minerals, vitamins, probiotic bacteria, as well as pharmaceutical actives. The unique helical structure of the amylose molecule, for example, makes starch a very efficient vehicle for encapsulating lipids and flavors (Conde-Petit et al., 2006). Some carbohydrates such as inulin and trehalose can provide additional benefits for encapsulation applications; inulin is a prebiotic that can enhance the survival of probiotic bacteria, while trehalose serves as support nutrient for yeasts.

Two main technologies–spray-drying and extrusion–are commonly used in large-scale encapsulation applications into amorphous matrices, although different mechanisms are used. In spray-drying, the active is entrapped within the porous membranes of hollow spheres, while in extrusion, the goal is to entrap the active in a dense, impermeable glass.

Encapsulating actives via spray-drying requires emulsifying the substrate into the encapsulating agent. This is especially important for flavor applications, considering the fact that most flavors are made of components of various chemistries (e.g., polarity, hydrophobic-to-hydrophilic ratios), thus limiting their stability when dispersed or suspended in different solvents. Hydrophobicity is one of the most critical attributes that can play a significant role in determining flavors payload as well as their release in food systems.

The basic principle of spray-drying can be found in an excellent book by Masters (1979). Briefly, the process comprises atomizing a micronized (1- to 10-µm droplet size) emulsion or suspension of an active and an encapsulating substance(s) and further spraying into a chamber. Drying takes place at relatively high temperatures (210 oC inlet and 90 oC outlet), although the active's exposure to these temperatures lasts only few seconds. The process results in free flowing, low bulk density powders of 10 to 100 µm. Optimal payloads of 20% can be expected for flavors encapsulated in starch matrices. Maltodextrins and lower molecular weight sugars, due to their low viscosities and inadequate emulsifying activities, often lead to lower flavor payloads.

Several factors can impact the efficiency of encapsulation via spray-drying, –mainly, those related to the emulsion or dispersion (e.g., solid content, molecular weight, emulsion droplet size, viscosity) and to the process (e.g., feed flow rate, inlet/outlet temperatures, gas velocity). Release of flavors from spray-dried matrices takes place on reconstitution of the dried emulsion in the release medium (water or saliva). Reasonable prediction of the release behavior should take into consideration the complex chemistry of flavors and prevailing partition and phase transport mechanisms between aqueous and nonaqueous phases (Larbouss et al., 1992; Shimada et al, 1991).

Encapsulation into an amorphous matrix via extrusion has gained wide popularity in the past two decades with applications ranging from entrapping flavors for their controlled release to masking the grittiness of minerals and vitamins. Hot melt extrusion is a process with many unique advantages for encapsulation applications, namely:

Extruders are multifunctional systems (many unit operations) that can be manipulated to provide desired processing temperature and shear rate profiles by varying screw design, barrel heating, mixing speed, feed rate, moisture content, plasticizers, etc.

There is the possibility of incorporating actives and other ingredients at different points of the extrusion process. Heat-labile actives, for example, can be incorporated via temperature-controlled inlets toward the end of the barrel, and their residence time in the extruder can be minimized to avoid degradation of the active and preserve its integrity.

Extruders are also formers; encapsulated products can be recovered in practically any desired shape or size (pellets, rods, ropes, etc.).

Only a very limited amount of water is needed to transform carbohydrates from native crystalline to amorphous glassy matrices in an extruder, thus limiting the need for expensive downstream drying.

High payload can exceed 30% when encapsulating solid actives in extruded pellets.

Favorable economics due to the high throughput, continuous mode, and limited need for drying make extrusion a very attractive process for manufacturing encapsulated ingredients.

Figure 1.1 shows a typical melt extrusion encapsulation process. The carbohydrate (encapsulating matrix), a mixture of sucrose and maltodextrin, is dry fed and melted via a combination of heat and shear in the extruder barrel so that the crystalline structure is transformed into an amorphous phase. The encapsulant (flavor or other active) is added through an opening in a cooled barrel situated toward the die end of the barrel to avoid flashing off of low boiling components. The amorphous mixture exits the die in the form of a rope that can be cooled quickly by air or liquid nitrogen to form a solid glassy material. The latter can be ground to a desired particle size to form compact microparticles of high bulk density. Using this technology, encapsulated products can be designed to achieve almost any desired target glass transition temperature by incorporating plasticizers (reduce Tg) or high molecular weight polymers (increase c01-math-0002 ).

Image described by caption/surrounding text.

Figure 1.1 Typical hot-melt extrusion system

(courtesy of Siemens, AG).

It should be cautioned, however, that although glass transition (and therefore microcapsule stability) is clearly related to the material properties of the matrix and rates of crystallization, there is growing evidence that in the glass transition region, small molecules are more mobile than might be expected from the high viscosity of the matrix (Parker and Ring, 1995). The mechanism of degradation of molecules entrapped in a glassy matrix is not fully understood but is speculated to be due to side chain flexibility and/or diffusion of small molecules such as water and oxygen through the glassy matrix. Other deteriorative mechanisms may include Maillard reaction between the active and the carrier matrix.

Microcapsules manufactured via extrusion and spray-drying may show structural imperfections, thus limiting their shelf-life. The latter is manifested in undesirable handling properties such as stickiness and clumping. The presence of exposed actives on the microparticle surface may have detrimental consequences such as drifts in the release profile and/or loss of active due to oxidation and other deteriorative processes.

A limited number of applications have used freeze-drying or similar evaporative techniques to form carbohydrate glasses from solution where the removal of water molecules takes place via either freezing the solution and subliming the ice as in freeze-drying or evaporation. Freeze-drying forms porous substrates due to transport of water vapor. Unlike starches, sugars lack fixed molecular structure and, thus, collapse on freeze-drying.

Co-crystallization with sugars has been practiced in few unique situations but has not found any commercial success. While crystalline sucrose is a poor flavor carrier, its co-crystallization with flavors forms aggregates of very small crystals, which can incorporate flavors via either inclusion within the crystals or entrapment between them.

Release of actives from amorphous carbohydrate matrices takes place by subjecting the matrix to moisture or high temperatures (i.e., by bringing the matrix to a temperature above its glass transition temperature). Microcapsules entrapped in amorphous structures are preferred for their ease of manufacturing, scalability, and economics compared with other encapsulation technologies. Their use has been adapted to a variety of food systems such as surface sprinkle on breakfast cereals, hot instant drinks, soups, teabags, chewing gum, pressed tablets, etc.

Complexation into cyclodextrins

Entrapment of actives into cyclodextrins is a unique approach to microencapsulation that is based on molecular selectivity. Cyclodextrins are cyclic oligosaccharides formed of various numbers of c01-math-0003 subunits with the 6-, 7-, and 8-numberd cyclic structures referred to as c01-math-0004 , and c01-math-0005 , respectively; these molecules vary in their solubility, cavity size, and complexation properties.

The type and degree of complexation in cyclodextrins are determined by two main factors: (1) steric fit of the guest (encapsulant) to the host (cyclodextrin) and (2) thermodynamic interactions, mainly hydrophobic interactions of the guest molecule with the host. Generally, one guest molecule can be included in one cyclodextrin molecule, although for some low molecular weight molecules, more than one guest molecule may fit into the cavity. For molecules with large hydrodynamic radii, more than one cyclodextrin molecule may bind to the guest. In principle, only a portion of the molecule must fit into the cavity to form a complex (Figure 1.2). As a result, 1:1 molar ratios are not always achieved, especially with very high or very low molecular weight guests.

Image described by caption/surrounding text.

Figure 1.2 Molecular complexation with cyclodextrin.

Guest molecules in cyclodextrins are not permanently entrapped, but they occur in a dynamic equilibrium. However, once a complex is formed and dried, it is very stable and often results in a very long shelf-life (up to years at ambient temperatures under dry conditions). Release of the complexed guest takes place by immersing the guest–host complex in aqueous media to dissolve the complex and further release of the guest when displaced by water molecules.

A wide variety of molecules can be entrapped in cyclodextrins, such as fats, flavors, colors, etc. (Martin Del Valle, 2004; Parrish, 1988). Complexation of cyclodextrins with sweetening agents such as aspartame, stevioside, and glycyrrhizin can stabilize these sweeteners and improve their taste as well as eliminate the lingering bitter aftertaste. Cyclodextrins can also be used to entrap undesirable substances such as cholesterol to rid milk, butter, and eggs from this undesirable component (Hedges, 1998; Szetjli, 1998).

Encapsulation in microporous matrices: physical adsorption

Physical adsorption can only be feasible when an active is adsorbed onto a high-surface-area microporous substrate, commonly referred to as molecular sieves. Cheremisinoff and Morresi (1978) cited two main examples of this category: activated carbon c01-math-0006 and amorphous silica c01-math-0007 . The effectiveness of these materials is demonstrated by the extensive reduction in equilibrium vapor pressure that accompanies physical adsorption of volatile flavors. Despite their efficiency in entrapping volatiles, silica and activated carbon use in foods has been discouraged due to regulatory constraints and is currently limited to packaging applications.

Micronized sugars have been used but with limited success in adsorption applications. Dipping capillary-sized droplets of sucrose or lactose solution into liquid nitrogen followed by freeze-drying can produce amorphous spheres that have the ability to adsorb aromas. Sorption of vapor causes these materials to revert to the more stable crystalline state with accompanying loss of porosity.

Encapsulation in fats and waxes

Solid particles can be encapsulated in fats or waxes to form reservoir or matrix-type microcapsules by using fluid bed coating or spray chilling techniques, respectively. These technologies are discussed in greater detail in Chapter 8 dealing with encapsulation of bakery leavening agents.

Fluid bed coating is a versatile encapsulation technology where a fat (or aqueous) coating can be applied to particles that are suspended in a temperature- and moisture-controlled chamber. For aqueous or solvent-based coating, an evaporation mechanism is necessary to form a dry coating; for fat-based coating, the molten fat is cooled to solidify the fat film around the coated particles. Multiple layers of fat/wax coating can be applied depending on the goal of encapsulation whether for controlled/targeted release or for taste masking.

In spray chilling, on the other hand, a dispersion of solid particles in a molten matrix is formed and is further sprayed through a nozzle into a cooled chamber to solidify the fat matrix. Despite its benefits in delayed-release applications, spray chilling results in the formation of small spherical particulates with a significant proportion of the active exposed to the outer surface of the particulate. This problem can be minimized by choosing process conditions where the active can bind tightly to the fat matrix or by applying an outer coating using a fluid bed coating system.

Encapsulation in emulsions and micellar systems

Micelles are described as reservoirs or microcontainers that entrap insoluble actives for their release at a targeted site, often via diffusional processes. The technique is simply an entrapment of a hydrophobic active in a hydrophilic shell material, thus enhancing the encapsulated particle or droplet solubility. This is no trivial matter when considering problems with bioavailability of many drugs and nutritional actives (fat-soluble vitamins, fish oil, and a host of water-insoluble drug actives). A second important aspect of micelles is their small size, which allows them to evade the body's screening mechanism, the reticuloendothelial system. Recognition by the reticuloendothelial system is the main reason for removal of many drug-delivery vehicles from the blood before reaching their target site (Sagaowicz et al., 2006). An in-depth discussion on encapsulation into micelles and emulsion systems can be found in Chapters 6 and 7 of this book by Dr Zuidam et al. and Professor Garti et al., respectively.

Despite the desirable structural characteristics of liposomes for encapsulation applications, one major challenge that often remains unresolved is liposome physical instability, especially during large-scale production and long-term storage (Chaudhury et al., 2012; Chen et al., 2010; Yokota et al., 2012). Lyophilization in the presence of cryoprotectants has been introduced recently as an alternative solution for improving liposome stability. Chaudhury et al. (2012) reported on lyophilizing cholesterol-free PEG liposomes containing the drug carboplatin to a moisture content of ∼2.6%, which resulted in a 2-fold increase in the drug loading with no measurable changes in their in vitro release profile compared with their nonlyophilized counterparts. A recent study by Stark et al. (2010) on optimizing conditions for lyophilizing extruded unilamellar liposomes showed that a mixture of glycerol and carbohydrate concentrations of ∼1% (w/v), irrespective of the carbohydrate composition, resulted in no significant changes in the bilayer organization, and the transition behavior of lipids during freezing.

Despite the promising data available on the benefits of lyophilization in preserving liposomes' structural integrity and bioavailability of encapsulated actives, this technique is still considered a work in progress and more research is needed to use this technology more effectively, especially in food and health ingredients applications. A broader discussion on lyophilized liposome technology can be found in Chapter 4 by Drs. Pinho and Tamiaso.

Encapsulation in coacervated polymers

Coacervation, as defined by Speiser (1976), is a process of transferring macromolecules with film properties from a solvated state via an intermediate phase, the coacervation phase, into a phase in which a film is formed around each particle and then to a final phase in which this film is solidified or hardened. Two types of coacervation processes are commonly used in encapsulation applications, namely simple and complex:

Simple coacervation is based on salting out of one polymer by the addition of agents (e.g., salts, alcohols) that have higher affinity to water than the polymer. It is essentially a dehydration process where separation of the liquid phase results in the solid particles or oil droplets becoming coated and eventually hardened into microcapsules.

Complex coacervation, on the other hand, is a process whereby a polyelectrolyte complex is formed. It requires the mixing of two colloids at a pH at which one is negatively charged and the other is positively charged, leading to phase separation and formation of enclosed solid particles or liquid droplets (Rabiskova and Valaskova, 1998).

Several parameters can impact the formation and integrity of coacervates, such as polymer molecular weight, temperature, and processing time. Core materials suitable for coacervation are solids and liquids that are water insoluble so that the active would not dissolve in the aqueous phase. High oil payloads (65–85%) were reported when using surfactants with hydrophilic-to-lipophilic balance (HLB) of 1.8–6.7. Using Tween 61 (HLB 9.6) reduced the oil payload, and Tween 81 (HLB 10) resulted in capsules with no oil entrapped (Rabiskova and Valeskova, 1998). Release of actives from coacervated systems is primarily a function of the wall type and its thickness (i.e., slower release with increased wall thickness). Chapter 3 of this book by Dr. Thies presents an in-depth discussion on complex coacervation phenomenon and its applications in encapsulation.

Encapsulation using supercritical fluids

Supercritical fluid (SCF) technology has been used effectively in extracting delicate essences and flavor components due to the process mild extraction conditions and the SCF's unique physicochemical properties. SCFs behave as intermediates between those of liquids and gases. They have similar densities in gas and liquid forms; their viscosities are near that of a gas with an almost zero surface tension, thus allowing their easy diffusion through highly porous nanostructures. Supercritical carbon dioxide (SC-CO2) is considered the most suitable substance for food and drug applications due to its low toxicity, low cost, easy removal, and nonflammability (Bahrami and Ranjibarajan, 2007; Brunner, 2005)

Encapsulation of thermolabile actives using SCF technology is a relatively new introduction to the field of microencapsulation (Chattopadhyay et al., 2006; Cocero et al., 2009; Fraile et al., 2014; Martin and Cocero, 2008; Sanli et al., 2012; Xia et al., 2011). The process consists of applying a polymeric thin film onto particles via simultaneous nucleation of the polymeric material out of a supercritical fluid, encapsulating the particles fluidized in the supercritical fluid, and further curing and binding the material coated on the particles (Silva and Meireles, 2014). One of the important parameters for the successful encapsulation using SCF technology is ensuring the solubility of the active and the polymer matrix in the supercritical fluid. Natural food-grade polymers such as modified starches, dextrins, and inulin have been used successfully in supercritical fluid encapsulation processes.

Supercritical fluid processing has been adapted to encapsulating various health ingredients and actives such as lutein, bixin, c01-math-0008 , astaxanthin, and other carotenoids (Chattopadhya and Gupta, 2002; Martin et al., 2007; Miguel et al., 2008; Xia et al., 2012), plant extracts such as rosemary (Carvallo et al., 2005), cholecalciferol, vitamin D3 (Xia et al., 2011), and quercetin (Fraile et al., 2014). A more elaborate discussion on microencapsulation via supercritical fluids can be found in Chapter 2 of this book by Dr. Cocero and co-workers.

Encapsulation into hydrogel matrices

Hydrogels are hydrophilic three-dimensional network gels that can absorb much more water than their own weight. Hydrogels consist of (a) polymers, (b) molecular linkers or spacers, and (c) an aqueous solution. Basic high molecular weight polymers include polysaccharides, proteins, chitin, chitosans, hydrophilic polymers, and others (Shahidi et al, 2006). The affinity of hydrogels to aqueous media makes them ideal absorbing matrices for food and agricultural actives.

Encapsulation by hydrogels is simply an entrapment of an active substance in a gel phase for its release in response to external stimuli. Release from hydrogels takes place via diffusion that can be affected by various chemical and physical factors. While chemical factors include H-bonds, ionic bonds, electrostatic interactions, and hydrophobic interactions between the active and matrix, physical factors include molecular size and conformation. Controlling (extending) the release of an active in a hydrogel matrix can be achieved by decreasing the hydrophilicity and/or diffusivity of the hydrogel structure or by covalently linking the active to the carrier hydrogel matrix.

Ideal hydrogels display a sharp phase transition on swelling in an aqueous solvent in response to environmental stimuli such as temperature, pH, electric field, etc. Release from hydrogels can be predicted from their lower critical solution temperatures (LCT) values. As temperature increases to the hydrogel's LCT, the hydrogel shrinks due to dehydration. Below LCT, hydrogels can take up water, thus increasing their swelling (Ichikawa et al., 1996). Grahm and Mao (1996) categorized the types of materials that cannot be delivered via hydrogels as those actives that are either (1) extremely water soluble due to the risk of uncontrollable quick release and (2) very high molecular weight substances due to the extremely slow release rate to achieve a desired benefit.

Encapsulation using flow-focusing technology

Production of uniform sized microparticles and nanoparticles is a primary challenge in many encapsulation processes. Given the importance of particle size in predicting release rate, research efforts have been centered on finding new methods suitable for producing monodisperse particles. One approach involves the use of hydrodynamic flow-focusing technology. This technology has been used for years by the ink jet industry and in diagnostic and detection assays but has only recently been adapted to encapsulation applications for the first time by Dr. Alfonso Gañán-Calvo at the University of Seville, Spain.

Flow focusing is in essence a laminar-jet disintegration technology that uses a combination of a specific axisymmetric geometry and hydrodynamic forces to produce droplets of uniform sizes (Freitas et al., 2005; Herrada-Gutierrez et al., 2010). The basic principle of flow focusing involves coaxial focusing of two or more immiscible fluid streams through a small opening where the outer continuous phase is set at a flow rate much higher than the inner disperse phase (Figure 1.3). After passing through the orifice, the central stream is forced to break up into droplets, due to a rapid change in fluid pressure and the prevailing shear stress of the outer continuous phase. To generate microparticles, the droplets often consist of liquid containing dissolved polymers. Once formed, these droplets rapidly undergo the additional step of solvent extraction or solvent evaporation, during which each turns into a particle or microsphere (Schneider et al., 2008). On curing, the drops can form multilayer microcapsules with multiple shells of controllable thickness. Flow-focusing technology is claimed to be scalable by replicating an arbitrary number of flow-focusing heads into an array structure that can result in the formation of monodisperse microencapsulated spheres.

Image described by caption/surrounding text.

Figure 1.3 Schematic diagram of (a) flow-focusing microfluidic process for making calcium alginate beads, (b) top view of the flow-focusing channels, C and D, as they pass through the orifice and the subsequent generation of microparticulates (from Hong et al., 2007, with permission).

Several advantages have been cited for flow focusing, such as (i) the ability to form monodisperse particles via adjusting flow rates of the two phases, (ii) mild process conditions that allow safe processing of thermolabile actives and (iii) reduction/elimination of clogging of particles exit holes due to the fact that liquid jets do not touch the exit holes, and (iv) unlike other encapsulation dripping techniques, the droplet size is not limited by the orifice diameter. Flow focusing has not yet proved its benefits in encapsulating foods and nutraceuticals actives due to challenges with throughput and high cost.

Overview of controlled-release systems

Despite the far-reaching applications of encapsulation and controlled-release technologies in many industries, predicting the release of encapsulated actives, especially in biological systems (foods included) remains a challenge. In the human gastrointestinal intestinal tract, for example, the release of microcapsules is a function of not only the microcapsule design and composition but also the physiological conditions, the presence of food, and the physicochemical properties of the ingested dosage.

One of the essential requirements for predicting release mechanisms of microencapsulated dosages is identifying parameters involved in mass-transport and diffusion of the actives from a region of high concentration (dosage) to a region of low concentration in the surrounding environment. Encapsulation and controlled release systems can be classified into: (a) matrix and (b) reservoir, or (c) their combination (Figure 1.4). It should be noted that in either system, the active is not covalently enclosed in the polymer matrix.

Image described by caption/surrounding text.

Figure 1.4 Typical microencapsulation systems: matrix, reservoir, and their combination.

Matrix systems

In a matrix or monolithic delivery system, the active is dispersed or dissolved within a rate-controlling polymer matrix. Such systems can best be represented by microparticles prepared by extrusion or fat-congealed capsules (spray-chilled) where the active is uniformly dispersed in the encapsulating medium (carbohydrate, fat, or other matrices). Matrix systems can be swellable (hydrogel) or nonswellable. In such systems, release is controlled by diffusion from the matrix through small pores. Some active particles or droplets lodged at the surface of the microcapsule will be readily released, leading to a small burst effect. However, diffusion of the remaining active particles located inside the microcapsule takes place at a slower pace as they need to travel a longer distance before they are released from the delivery device. Application of a coating material over a monolithic microparticle can help eliminate burst release, although it might change the release profile. Other treatments include washing microparticles to extract active particles exposed to the microcapsule surface. Compared with reservoir systems, matrix systems require less quality control and, hence, lower manufacturing cost.

Reservoir systems

Reservoir systems are simply described as delivery devices where an inert membrane surrounds an active agent that, on activation, diffuses through the membrane at a finite controllable rate (Siepmann et al., 2012). The active's release rate is mainly a function of the physicochemical properties of the active and the polymer (e.g., thickness, molecular weight, integrity, etc.). In reservoir systems, the purpose of the membrane is to mediate diffusion of the active; therefore, release of the active takes place via its initial partition into the surrounding membrane followed by diffusion. Because of their simple mechanism and ability to produce zero-order release, reservoir systems would seem to be highly advantageous. However, these systems can be difficult to fabricate reliably and often small defects or cracks in the membrane lead to dose dumping as discussed above, release of actives from a reservoir-type system is controlled by the physicochemical properties of the encapsulating polymer (e.g., composition, molecular weight, etc.) and the active (e.g., molecular weight, particle size, solubility, etc.).

Combination systems

Examples of this category can best be illustrated by congealed microcapsules or extruded microparticles with additional coating (enrobing) film. This technique is most useful for manufacturing extremely delayed-release profiles.

Release mechanisms

In designing microcapsules for controlled-release applications, it is critical to identify the desirable release profile so that adequate materials and technology can be chosen. The principal modes of controlled release are delayed, sustained, and burst release (Figure 1.5).

Image described by caption/surrounding text.

Figure 1.5 Principal modes of controlled release, burst, delayed, and sustained.

In the delayed-release mode, the release of an active substance is delayed from a finite lag time up to a point where its release is favored and is no longer hindered. Examples of this category include encapsulating probiotic bacteria for their protection from gastric acidity and subsequent release in the lower intestine, flavor release on microwave heating of ready-meals, or the release of encapsulated sodium bicarbonate on baking of a dough or cake batter.

Sustained release, on the other hand, aims at maintaining the release of constant concentrations of an active at its target site for a desired time. Examples of this mode include encapsulating flavors and sweeteners for chewing gum applications so that their rate of release is maintained throughout the time of chewing.

Burst release is simply described by a high initial delivery of an entrapped active. This type of release is desirable for delivering instantaneous burst of flavors or fragrances. However, it may be detrimental to other systems such as encapsulated drugs and may lead to high toxicity levels and ineffective administration of the drug.

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Chapter 2

Encapsulation of edible active compounds using supercritical fluids

Salima Varona, Ángel Martín and María José Cocero

Supercritical fluid technology

Properties of supercritical fluids

A supercritical fluid (SCF) is a substance that is above its critical temperature c2-math-0001 and critical pressure c2-math-0002 (e.g., c2-math-0003 ). The critical point represents the highest temperature and pressure at which the substance can exist as a vapor and liquid in equilibrium. The supercritical region can be represented in the phase diagram of CO2 as shown in Figure 2.1. One of the main advantages of SCFs compared with conventional solvents is their compressibility. This property of SCFs along with the ability to modify densities of such solvents via small changes in pressure when in the supercritical region can lead to considerable flexibility in their properties (Brunner, 1994).

Image described by caption/surrounding text.

Figure 2.1 Phase diagram pressure vs. temperature and volume vs. pressure. CP, critical point; TP, triple point.

Physical properties of SCFs are often described as intermediates between those of a liquid and a gas. SCFs can show densities similar to those of liquids but viscosities, thermal conductivities, and diffusivities comparable to those of gases (Table 2.1). While liquid-like solvent properties are beneficial for drug solubilization, polymer plasticization, and extraction of organic solvents or impurities, gas-like transport properties are important for enhancing the mass transfer and promoting the selectivity of extractions or reactions. SCFs are able to spread out along a surface more easily than liquids due to their lower surface tensions. Further, the properties of SCFs can be adjusted to the needs of a process via temperature and pressure variations, as shown in the example depicted in Table 2.1.

Table 2.1 Comparison between the orders of magnitude of the properties of liquids, gases, and supercritical fluids

In pharmaceutical and food applications, supercritical CO2 (SC-CO2) is the most