Characterization and Stability

Subsequent chapters provide many examples of suspensions in industry and everyday life. Solid suspensions and dispersions of one solid in another solid, are not, in general, covered in this book. 

The next four chapters provide an introduction to the concepts and techniques needed to study and understand dispersion stability. Some approaches to the characterization of emulsions, foams and suspensions, and of their dispersed species (droplets, bubbles and particles)are described in Chapter 2. The concepts of surface tension, wettability and surface activity, which are important to the stability and properties of all types of dispersion, are described in Chapter 3. To this is added the nature of electrically charged surfaces in Chapter 4. All of these aspects are brought together in Chapter 5 in an introduction to the stability of dispersions. 

Some complex dispersions do not fit neatly into the earlier classical distinctions. For example, anti-bubbles are dispersed species of liquid-in-gas-in-liquid wherein a droplet of liquid is surrounded by a thin layer of gas that in turn is surrounded by bulk liquid. In an air-aqueous surfactant solution system, such a dispersion would be designated as water-in-air-in-water, or W/AAX/ , in fluid film terminology. Some examples are provided in Reference [83]. 

Colloidal liquid aphrons are a kind of emulsion in which micrometre-size dispersed droplets have an unusually thick stabilizing film and exist clustered together as opposed to either separated, nearly spherical droplets. The stabilizing aqueous film, sometimes called a soapy shell, is thought to have inner and outer surfactant monolayers. Taking this a step further, vesicles are droplets characterized by the presence at their surface of a lipid bimolecular film (bilayer) or series of concentric bilayers. A vesicle can be single or multilamellar and stabilized by natural or synthetic surfactants. Vesicles made from lipid or fat (e.g. phospholipid) bilayers are called liposomes (or, sometimes,/jofyso/wes). 

For lyophobic dispersions, which are not thermodynamically stable, the degree of kinetic stability is very important (see Section 5.5). A complete characterization of colloid stability requires consideration of the different processes through which dispersed species can encounter each other sedimentation (creaming), aggregation and coalescence. Sedimentation results from a density difference between the 

Asimov, I. (1959) Words of Science and the History Behind Them, Riverside Press, Cambridge, MA. 

---

In vivo reproducible results can only be achieved if the liposome-drug or -antigen combinations are thoroughly characterized upon preparation in terms of their physical and chemical properties and, besides, if the stability during storage is ensured. In this chapter both the pharmaceutical (preparation, characterization, and stability) aspects and the therapeutic potentials and limitations of drug and antigen delivery with liposomes will be discussed. 

Crommelin, D. J. A., and Storm, G. (1987). Pharmaceutical aspects of liposomes Preparation, characterization, and stability, in Controlled Drug Delivery (B. W. Muller, ed.), Wissenschaftliche Verlagsgescellschaft mbH, Stuttgart, pp. 80-91,... 

Socaciu, C. et al.. Carotenoid-rich fractions in sea buckthorn berry oleosomes separation, characterization and stability in colloid supramolecular structures, Proc. 4th Int. Congr. Pigments in Food, October 9-12, 2006, Shaker Verlag GmbH, Stuttgart, Germany. 

This chapter describes the basic principles involved in the development of disperse systems. Emphasis is laid on systems that are of particular pharmaceutical interest, namely, suspensions, emulsions, and colloids. Theoretical concepts, preparation techniques, and methods used to characterize and stabilize disperse systems are presented. The term particle is used in its broadest sense, including gases, liquids, solids, molecules, and aggregates. The reader may find it useful to read this chapter in conjuction with Chapters 8, 12, and 14, since they include some of the most important applications of disperse systems as pharmaceutical dosage forms [1]. 

Heindel, N.D., Zhao, H., Leiby, J., VanDongen, J.M., Lacey, C.J., Lima, D.A., Shabsoug, B., and Buzby, J.H. (1990) Hydrazide pharmaceuticals as conjugates to polyaldehyde dextran Syntheses, characterization, and stability. Bioconjugate Chem. 1, 77-82. 

A.K. Singh, A.W. Flounders, J.V. Volponi, C.S. Ashley, K. Wally, and J.S. Schoeniger, Development of sensors for direct detection of organophosphates. Part I immobilization, characterization and stabilization of acetylcholinesterase and organophosphate hydrolase on silica supports. Biosens. Bioelectron. 14, 703-713 (1999). 

Thus, the use of subzero temperatures in cryosolvents has allowed a series of intermediates in the elastase reaction to be identified, characterized, and stabilized. Temporal resolution of the significant steps in this reaction was difficult to achieve by any other method. Analogous results with other serine proteases suggest that these results are general for this class of enzymes. 

Szebeni J, Di lorio EE, Hauser H, et al. Encapsulation of hemoglobin in phospholipid liposomes characterization and stability. Biochemistry 1985 24 2827. 

Yu L. Amorphous pharmaceutical solids preparation, characterization and stabilization. Adv Drug Deliv Rev 2001 48 27-42. 

ITABLE 4.5. Some analytical techniques use in protein characterization and stability assessment... 

Shire, S. J. (1996), Stability, characterization and formulation of recombinant human deoxyribonuclease (Pulmozyme , Dornase Alpha), in Pearlman, R., and Wang, Y. J. Eds., Formulation, Characterization and Stability of Protein Drugs, Plenum Press, New York, pp. 393 126. 

Tan, C.P., Nakajima, M. (2005). fi-Carotene nanodispersions preparation, characterization and stability evaluation. Food Chemistry, 92, 661 -671. 

Yuan, Y., Gao, Y., Zhao, J., Mao, L. (2008). Characterization and stability evaluation of p-carotene nanoemulsions prepared by high pressure homogenization under various emulsifying conditions. Food Research International, 41, 61-68. 

Herman AC, Boone TC, Lu HS. Characterization, formulation, and stability of Neupogen (filgrastim), a recombinant human granulocyte-colony stimulating factor. In Pearlman R.WangYJ (Eds.), Formulation, Characterization, and Stability of Protein Drugs. New York, NY Plenum Press 1996 303-328. 

CRM is used, the provided uncertainty of the certibed analyte D including the uncertainty contribution of homogeneity, characterization, and stability D could be used as assigned standard deviation for probciency evaluation. In practice, this is seldom done. The common approach is to debne a bt-for-purpose criterion as... 

Vicent, E., Morallon, E., Quijada, C. and Vazquez, J.L. (1998) Characterization and stability of doped Sn02 anodes. J. Appl. Electrochem. 28, 607-612. 

Volkin, D. B., and Middaugh, C. R. (1996). The characterization, stabilization, and formulation of acidic fibroblast growth factor. In Formulation, characterization, and stability of protein drugs (R. Pearlman and Y. J. Wang, eds.), pp. 181-217. Plenum, New York. 

In this chapter we will provide information about the basic characteristics of liposomes staring from their building blocks, that is, phospholipids. After this, liposome structure, physicochemical properties, and stability, which are most important for their in vivo performance, will be discussed as well as methods used for liposome preparation, characterization, and stabilization. Following this first part which is more technological, we will move into the biological part and talk about the fate of conventional liposomes and sterically stabilized liposomes, as well as liposomal drugs, after in vivo administration by different routes [mainly intravenous (i.v.), intraperitoneal (i.p.), or subcutaneous (s.c.)] and also give some information about other possible routes for in vivo administration of liposomes. Finally, specific applications of liposomes in therapeutics will be presented, some in more detail, mainly for the therapy of different types of cancer. 

Bhalerao, S. S., and Harshal, A. R. (2003), Preparation, optimization, characterization, and stability studies of salicylic acid liposomes, Drug Dev. Ind. Pharm., 29,451 467. 

The introduction to the symposium details the current constraints on research in general and chemical modeling in particular. The 37 technical papers presented fall naturally into the areas of 1) redox equilibria, 2) organic ligand characterization and stability constant estimation, 3) adsorption processes, 4) evaluation and estimation of thermodynamic and kinetic data, 5) interfacing chemical and biological models, and 6) comprehensive chemical models and their applications. 

H. van Olphen, An Introduction to Clay Colloid Chemistry, for Clay Technologists, Geologists and Soil Scientists, 2nd ed., Wiley (1977). (Explains how colloid characterization and stability can be applied to clay minerals.)... 

Powell, M.F. A Compendium and hydropathy/flexibility analysis of common reactive sites in proteins reactivity at Asn, Asp, Gin, and Met Motifs in neutral pH solution. In Formulation, Characterization, and Stability of Protein Drugs Pearlman, R., Wang, Y.J., Eds. Plenum Press New York, NY, 1996 1-140. 

Roscic M, Horvat S (2006) Transformations of bioactive peptides in the presence of sugars - Characterization and stability studies of the adducts generated via the Maillard reaction. Bioorg Med Chem 14 4933 943 (vide penetus)... 

Connor, R. E., Nicholas, K. M. Isolation, characterization, and stability of a-[(ethynyl)dicobalt hexacarbonyl] carbonium ions. J. Organomet. Chem. 1977,125, C45-C48. 

Ugwu S et al (2005) Preparation, characterization, and stability of liposome-based formulations of mitoxantrone. Drug Dev Ind Pharm 31 223-229... 

Interesting case histories about formulation, characterization and stability of protein drugs are discussed in the book edited by Pearlman and Wang. ... 

Pinna, N., Weiss, K., Sack-Kongehl, H., Vogel, W., Urban, J. and Pileni, M.P. (2001) Triangular CdS nanocrystals Synthesis, characterization, and stability. Langmuir, 17, 7982-7987. 

---