Filling a gap in the literature, this is the first book to focus on the fabrication of functional porous materials by using ice templating and freeze drying.
Comprehensive in its scope, the volume covers such techniques as the fabrication of porous polymers, porous ceramics, biomimic strong composites, carbon nanostructured materials, nanomedicine, porous nanostructures by freeze drying of colloidal or nanoparticle suspensions, and porous materials by combining ice templating and other techniques. In addition, applications for each type of material are also discussed.
Of great benefit to those working in the freeze-drying field and researchers in porous materials, materials chemistry, engineering, and the use of such materials for various applications, both in academia and industry.
Dr Haifei Zhang is a senior lecturer in the Department of Chemistry at the University of Liverpool. Zhang was educated in chemical engineering for both undergraduate and Master degrees and obtained a PhD in physical chemistry from Chinese Academy of Science in 2001. He has published over 90 peer reviewed research articles and filed 9 international patents as a co-inventor. He won the 12th Desty Memorial Award in 2007 for his innovative work in the manufacture of porous materials and their applications in chromatography. Zhang?s main research interests are on porous materials and nanostructured materials for nanomedicine, separation, and energy storage.
Introduction to Freeze-drying and Ice Templating
Freeze-drying is a widely used drying technique in pharmaceutics, biologics, and food industries. It is a preferred drying technique when dealing with temperature-sensitive chemicals/substances, as it can produce dry powders or cakes for easy storage and transport. From the perspective of pharmaceutical applications, the freeze-dried products should also have a reasonable shelf life and be readily reconstituted with the anticipated drug activity [1-4].
A freeze-drying process, especially for pharmaceutics and biologics, consists of three steps, i.e. freezing on a cold shelf in a freeze-dryer chamber, primary drying, and secondary drying [1, 4]. The freeze-drying process is usually applied to aqueous solutions or suspensions. When freezing aqueous solutions or suspensions (usually in small vials), the majority of the water in the sample is either free water or gets frozen. However, a small percentage of the water bound to or having strong interaction with pharmaceutics/excipients remains as liquid. The amount of liquid water present in the frozen sample depends on the freezing temperature as well as the components in the solution. The frozen ice crystals are sublimed in the primary drying process, i.e. a change from solid state to vapour state to remove the ice crystals. In the secondary drying step, the bound water needs to diffuse and transport outside of the porous matrix to be removed. Therefore, the rate of primary drying may be controlled or enhanced by careful control of the freezing temperature, the shelf temperature, and the vacuum, whilst the nature and the porosity of the matrix is more important for the secondary drying stage.
In chemistry, biological and materials research, freeze-drying is more commonly known as a drying approach. The cool samples may be either directly placed on a shelf in a freeze-dryer or frozen in a freezer or in liquid nitrogen before being placed into a freeze-dryer. The main purpose is to keep the samples at low temperature (to maintain the component activity) and to prevent dense aggregation or considerable shrinkage during the drying process. This is in contrast to a conventional drying process of aqueous solution or wet samples, e.g. drying in open air, N2 flow drying or vacuum drying. Because of water's high surface tension, removing liquid water can generate significant surface force that brings small particles together (hence aggregation of particles) or the collapse of porous structure. For this reason, freeze-drying has been frequently used in materials science in order to prepare materials with highly interconnected porosity and high surface areas.
During a freeze-drying process, either in a pharmaceutical industry environment or in a research lab practice, the process needs to be conducted so that the samples remain frozen, avoiding partial melting and annealing, following which porous cakes or structures without dense skin and shrinkage are prepared. This is, of course, not just intended to produce a material with an 'aesthetic look' . Such materials can have desirable properties for subsequent applications. After the removal of ice crystals, the voids left behind are pores within the materials, hence the porous materials. In the pharmaceutical industry and other relevant research areas, good cakes with homogeneous structures are desirable for their subsequent applications. The porous structures of such cakes are examined with the intention of relating the quality of the freeze-dried materials with subsequent application performance, rather than as a technique to prepare porous materials with controllable porosity and morphology.
Porous materials are used in a wide range of applications and have been intensively investigated [5, 6]. According to the IUPAC definition, the pores can be categorized as macropores (>50?nm), mesopores (2-50?nm), and micropores (<2?nm) . Templating is probably the most common approach used for the preparation of porous materials. The templates used may be hard templates (e.g. colloids, particles, sacrificial pre-formed porous structures) or soft templates (e.g. assembly of surfactants, polymers, droplets, emulsions) . In recent years, ice templating has been developed and intensively investigated as an effective approach to the production of a variety of porous materials [8-11]. This templating method exhibits some unique characteristics that the other techniques do not have. For instance, a directional freezing process can be employed to prepare aligned porous materials. By careful control of the freezing conditions, layered porous materials can be formed and can be subsequently utilized to produce tough composite materials mimicking natural structures. Furthermore, the ice templating method is not restricted to water-based solutions or suspensions. It can be used for organic solutions/suspensions, compressed CO2 solutions, and emulsions .
Sometimes, there is a misconception that freeze-drying and ice templating may be the same, as seen in some published articles. However, they are different but are related with each other. In brief, freeze-drying is a drying method (in pharmaceutical industry the freezing process is usually completed on the freeze-dryer shelf). Figure 1.1 shows the schematic representation of a freeze-drying process. Ice templating is a templating method where ice crystals are used as templates in order to produce the desired templated structures. A controlled freezing process is usually required in order to control the orientation, size, and morphology of the ice crystals. As in any other templating methods for the preparation of porous materials, the ice templates need to be removed. The most common method to remove ice crystals is by freeze-drying. However, freeze-drying is not the only method that can be used. Solvent exchange may be employed in a cold miscible solvent (and it is an insoluble solvent to the solute in the frozen solvent) where the temperature is below the melting point of the frozen sample. After the frozen solvent is completely removed, the materials may be dried by usual drying methods such as air drying or vacuum drying. There is another option when monomers and crosslinkers or reactive reagents are included in the frozen samples. A frozen polymerization/crosslinking process can be applied, which will lock in the frozen structure . After polymerization, the frozen samples may be warmed up to room temperature and then dried in air or by vacuum drying.
Figure 1.1 Schematic representation of a freeze-drying process. The temperature and time scales are approximate and for indication only.
Because of the close link between freeze-drying and ice templating, in this chapter, we will first introduce the basics and key aspects/parameters of a freeze-drying process. The same controls applied in freeze-drying may be applied to the ice templating approach as well when ice crystals are removed by a freeze-drying process. However, it must be pointed out that there is very limited research on the effects of the freeze-drying process on porous materials or nanostructures. Secondly, the key aspects, important parameters and progress of ice-templating method will be covered. The practice and experience of the Zhang group in ice templating and freeze-drying for porous materials will be described last, hopefully to provide useful and practical information for researchers who are new to this research area.
1.2 The Freeze-drying Process
Water is essential for life. However, the presence of water tends to make materials or products degrade fast. To preserve samples, to make storage longer and transport easier, suitable drying methods are required. This is particularly important for biological and pharmaceutical samples. Indeed, freezing itself is a drying technique. During the freezing process, water turns into ice crystals, which can exclude any impurities, including polymers, particles, and dissolving molecules. The freezing front rejects the solutions from forming ice crystals; this concentrates the solution and makes the dissolved substances 'dry'. However, the frozen 'dry' samples have to be kept at low temperature (below the melting point) and are normally stored in a freezer. This incurs storage costs and difficulty in transporting. Potential freezer break down or power cut can melt and damage the samples. Thus, a freeze-drying process is a preferred drying process.
The use of freeze-drying has a long history, tracing back to 1250 BCE for preserving materials by dehydrating, which involves the freezing stage and drying at low temperature under vacuum. Freeze-drying is also widely known as 'lyophilization', a term mostly attributed to Rey LR's work in 1976. Because the process produces a dry porous structure, its high porosity and exposed surface can rapidly resorb the solvent, e.g. the water, vapour or moisture in the surrounding environment. The freeze-dried materials exhibit such 'lyophil' characteristics towards the solvent (mostly water), hence the term 'lyophilization' process .
But it is not all positive for a freeze-drying process. The disadvantages associated with freeze-drying processes are low scale-up potential,...