Inorganic Controlled Release Technology -  Mark Cresswell,  Xiang Zhang

Inorganic Controlled Release Technology (eBook)

Materials and Concepts for Advanced Drug Formulation
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2015 | 1. Auflage
264 Seiten
Elsevier Science (Verlag)
978-0-08-100006-9 (ISBN)
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Inorganic Controlled Release Technology: Materials and Concepts for Advanced Drug Formulation provides a practical guide to the use and applications of inorganic controlled release technology (iCRT) for drug delivery and other healthcare applications, focusing on newly developed inorganic materials such as bioresorbable glasses and bioceramics. The use of these materials is introduced for a wide range of applications that cover inorganic drug delivery systems for new drug development and the reformulation of existing drugs. The book describes basic concepts, principles, and industrial practices by discussing materials chemistry, physics, nano/microstructure, formulation, materials processing, and case studies, as well as the evaluation and characterization of iCRT systems commonly investigated during industrial R&D.


  • Provides the first book on inorganic controlled release technology (iCRT), covering key aspects from chemistry, physics, synthetic methods, formulation design, characterization and evaluation
  • Includes several industry-related case studies to provide practical guidance on how to use iCRT as an alternative to organic polymers systems for both future drug developments and other active ingredient applications
  • Demonstrates how iCRT offers an unmet business need for improved, controlled release of actives versus traditional CRT systems, which are known to have difficulty with the controlled delivery of both poorly and highly water soluble drug compounds


Dr Xiang Zhang, the Royal Society Industry Fellow at University of Cambridge, is a materials scientist and one of the leading biomaterials and medical devices experts in the world with 33 years combined experience, 17 years in academia and 16 years in industry. He places particular emphasis on carrying out fundamental but applied research as he believes that this in depth fundamental understanding of specific scientific issues is the key to the design and development of successful medical products for industry to benefit society. Dr Zhang undertook his PhD and postdoctoral research at Cranfield University where he studied materials physics and nano-fracture mechanics of organic and inorganic hybrid materials and developed new materials for ICI the largest chemical manufacturer in Britain at that time. He was awarded an industrial fellowship at the University of Cambridge in 1995. His industry experience was gained at Abbott in 1999, where, as Principal Scientist, his work covered almost all aspects of medical materials and devices from R&D and manufacturing. Further industrial experiences were gained with Cambridge NanoTech and Lucideon as Consultant Director and Principal Consultant respectively, working for worldwide clients to provide materials solutions for pharmaceutical companies and research institutes.
Inorganic Controlled Release Technology: Materials and Concepts for Advanced Drug Formulation provides a practical guide to the use and applications of inorganic controlled release technology (iCRT) for drug delivery and other healthcare applications, focusing on newly developed inorganic materials such as bioresorbable glasses and bioceramics. The use of these materials is introduced for a wide range of applications that cover inorganic drug delivery systems for new drug development and the reformulation of existing drugs. The book describes basic concepts, principles, and industrial practices by discussing materials chemistry, physics, nano/microstructure, formulation, materials processing, and case studies, as well as the evaluation and characterization of iCRT systems commonly investigated during industrial R&D. Provides the first book on inorganic controlled release technology (iCRT), covering key aspects from chemistry, physics, synthetic methods, formulation design, characterization and evaluation Includes several industry-related case studies to provide practical guidance on how to use iCRT as an alternative to organic polymers systems for both future drug developments and other active ingredient applications Demonstrates how iCRT offers an unmet business need for improved, controlled release of actives versus traditional CRT systems, which are known to have difficulty with the controlled delivery of both poorly and highly water soluble drug compounds

Chapter 2

Materials Fundamentals of Drug Controlled Release


Abstract


Understanding the interactions between an API (active pharmaceutical ingredient) and the other formulation constituents, not only in the bulk but also at the molecular level, is crucial in understanding the key properties of a formulation. This is especially the case when new controlled release formulations are being designed and prepared from first principles. Here we introduce the fundamental physical properties of inorganic controlled release technology (inorganic CRT) materials and the physical and chemical basis for their interactions with API molecules. A more detailed discussion of these theories, with the aid of relevant examples, highlights the benefits of using inorganic CRT materials for drug delivery formulations. Following this, an appreciation of how an understanding of these fundamentals can help in the design of new inorganic CRT formulations is highlighted. Finally, we introduce the theories involved with establishing the drug release kinetics of a novel inorganic CRT system and how the results gained from this kinetic analysis can provide useful information on the mechanism of drug release, which can then be used to feed back into the formulation design stage.

Keywords

Amorphous materials

Drug distribution

Drug-matrix interactions

Surface chemistry

inorganic CRT formulation roadmap

Molecular dispersion

Release kinetics

Contents

2.1 Introduction of Materials Nanostructure   17

2.1.1 The structure of amorphous materials   18

2.1.2 Theories of amorphous materials   21

2.1.2.1 Glass transition   21

2.1.2.2 Free volume theory   22

2.2 API Distribution Within Inorganic Matrices   23

2.2.1 Traditional API distribution   23

2.2.2 API distribution within inorganic CRT matrices   26

2.3 Basic Understanding of Potential Molecular Interactions   29

2.3.1 Classical API excipients   29

2.3.2 Interactions between API and inorganic CRT matrix systems   30

2.3.3 The surface chemistry of silica   32

2.3.4 Molecular interaction with directionally templated mesoporous silica systems   33

2.3.5 Towards molecular dispersion and distribution   38

2.3.6 Molecular interaction sites on sol-gel silica and phosphate glass   39

2.3.7 Dissolution of phosphate glass   45

2.3.8 Glass formulation for inorganic CRT   47

2.4 Theory and Practical Modelling of Drug Controlled Release Kinetics   48

References   53

Further reading   55

2.1 Introduction of Materials Nanostructure


In Section 1.2 materials chemistry and processing technology were introduced and discussed in the context of the two main production routes to make glass materials for controlled release applications, that is, fusion and sol-gel. Due to its cultural and historical significance the word ‘glass’ is ubiquitous in many publications and is synonymous with a certain type of glassy material based around soda-lime glass—container-ware and window glass being the most common examples. However, glassy materials made by the two different processes, fusion and sol-gel, have different structural properties as a consequence of the molecular process involved during their formation. To fully understand the fundamentals of inorganic controlled release technology (inorganic CRT) materials science, it will benefit the reader of the book to introduce the theories and fundamentals of amorphous materials, in particular, on the physical aspects.

2.1.1 The Structure of Amorphous Materials


There is a general consensus that the word ‘glass’ signifies only that transparent material, which is mainly made from silica plus small amounts of other oxides, and is used for producing windows. We will transform this simple understanding on transparent materials into fundamentals of amorphous materials in view of their nano/microstructure.

Amorphous materials are generally regarded as non-crystalline materials. They are not new; the iron-rich siliceous amorphous materials recovered from the moon by the Apollo mission are some billions of years old. The history of man-made amorphous materials, the glass from silica, has been known for at least several thousand years. Although the science of the materials chemistry is well established, the material physics is not so well studied and understood to date. There is growing interest in the fundamental science of amorphous materials because most recently there has been great interest for their use for novel applications and technological areas. Healthcare is one of these areas including the materials science and technology for inorganic CRT, discussed here.

In general, non-crystalline amorphous materials possess randomness to some degree. The questions are what kind of randomness is present, and what is the best way to define it? There needs to be a standard based on which we can define amorphous materials and their structure. This standard is the perfect crystal, with the following definition:

A perfect crystal is that in which the atom or group of atoms are arranged in a pattern that repeats periodically to infinite extent.

In this book, we regard the repeating periodicity that is in all three dimensions. However, two-dimensional (2D)1,2 and one-dimensional crystals3 have been reported, in order to simplify the classical definition of a perfect crystal. The basic element of the perfect crystal is an atom or group of atoms, upon which the structure of the perfect crystal is built starting at the nanometre scale and growing periodically by an infinite extent and ending at surfaces (non-infinite extent), or at a defect, that is, foreign atoms or a dislocation of the crystal.

Considering the standard definition of a perfect crystal, we now have the following definition for an amorphous structure:

An amorphous structure does not possess the long-range periodicity characteristics of a perfect crystal in that atoms or a group of atoms are arranged in a random pattern that cannot repeat periodically.

To understand the nature of long-range periodicity, Figure 2.1 shows schematically the periodicity of a perfect 2D crystal and the randomness of a 2D amorphous structure. It is seen that the non-crystalline structure consists of no translational periodicity (Figure 2.1b), which is in contrast to the crystalline structure where there is such translational periodicity (Figure 2.1a). Understanding the structural arrangement of atoms in a solid substance is essential for the understanding of its physical properties, and this is true for both crystalline and amorphous materials. Determination of a crystalline structure is made straightforward by measuring a ‘unit cell’, containing relatively few atoms in most cases. This unit cell is the fundamental building block upon which crystals are formed: by repeating in a periodical fashion the position of the unit cell in space. Such a procedure is impossible for a non-periodic amorphous solid, for which the unit cell is regarded as being infinitely large. Figure 2.2 shows a typical crystalline amorphous X-ray diffraction (XRD) profile, and Figure 2.3 shows an amorphous material XRD spectrum (detailed analysis of XRD will be introduced in Chapter 3).

Figure 2.1 Schematic representation of a 2D crystal (a) and a 2D amorphous structure (b).
Figure 2.2 Typical crystal WAXS profile: hydroxyapatite. (Courtesy of Lucideon X-ray Department).
Figure 2.3 Typical amorphous WAXS profile: sol-gel glass. (Courtesy of Lucideon X-ray Department).

The relative simplicity of the amorphous material XRD diffractogram belies the actual complexity of the system. The forms of randomness with which we are concerned create more uncertainty than a perfect crystal. Imaging the huge number of forms, scales and extents of amorphous randomness are all variables in view of the nanostructure. The structural variation of an amorphous material will at least affect the location, distribution, and interaction of any active ingredients present within the delivery matrices used in inorganic CRT applications.

In reality, the structure of amorphous materials is not complete randomness; they often have short-range order. Further still, some amorphous materials have considerable short-range...

Erscheint lt. Verlag 28.8.2015
Sprache englisch
Themenwelt Medizin / Pharmazie Gesundheitsfachberufe
Medizin / Pharmazie Medizinische Fachgebiete Pharmakologie / Pharmakotherapie
Medizin / Pharmazie Pharmazie
Naturwissenschaften Chemie Anorganische Chemie
Technik Maschinenbau
Wirtschaft
ISBN-10 0-08-100006-5 / 0081000065
ISBN-13 978-0-08-100006-9 / 9780081000069
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