Factors Affecting Physical Stability

We will first illustrate how chemical variables affect surface charge and surface potential. Then we will discuss more quantitatively a physical stability model which depends on the surface potential (which, in turn, has been determined by chemical factors). 

Several compositional and processing variables affect the physical stability of the casein micelles in frozen milk concentrates. These factors include pH, mineral composition, total solids content, forewarming treatment, homogenization and fat content, freezing rate, storage temperature, and fluctation of storage temperature (Keeney and Kroger 1974 Webb 1970). 

A tabulation of all the available physical constants of TNT, with refs, was published in 1952 (Ref 23). Included are thermodynamic and crystallographic data, solubilities, and factors affecting chemical stability. Of the 57 properties listed, 28 were selected as most important, and the best values are cited. Another useful compilation of physical properties appeared in 1971 (Ref 43), but with limited refs a revised edition is scheduled for about 1980. Both of these reports are limited in distribution, as is a data manual published in England (Ref 18). Compilations of physical and other properties appeared in 1972 (Ref 51) this report has unlimited availability... 

Some ofthe factors that affect the physical stability of emulsions include the type and concentration of surfactant used to stabilize the emulsion, the phase volume ratio (i.e., ratio of oil to aqueous phase), droplet size, compatibility of drug and excipients with the emulsion, and storage condition ofthe emulsion. 

Once good physical stability of an emulsion is insured, its commercialization mandates chemical stability of the incorporated drug and other essential components for at least 18 months. Key factors that affect the chemical stability of pharmaceutical emulsions include drug stability in oil, drug stability in aqueous media, drug concentration in oil and emulsion, phase volume ratio, droplet size, presence of excipients, and presence of air and/or peroxide radicals. As mentioned earlier, choice of appropriate antioxidant is important. 

P.F. Grassby, and L. Hutchings, Factors affecting the physical and chemical stability of morphine sulphate solutions stored in syringes. Int. J. Pharm. Pract. 2 39-43, 1993. 

B. S. Chang, R. M. Beauvais, A. Dong, and J. F. Carpenter, Physical factors affecting the storage stability of freeze-dried interleukin-1 receptor antagonist glass transition and protein conformation. Arch. Biochem. Biophys. 557 249-258 (1996). 

The object of this chapter is to provide some background for the appreciation of the pharmaceutics of proteins, peptides DNA, oligonucleotides and monoclonal antibodies as therapeutic entities. From an understanding of the nature of amino acids and their physical properties comes an appreciation of the physical nature and properties of peptides, polypeptides and proteins, defined below. The solution properties of proteins in simple and complex media should be understood, together with the factors affecting the stability of proteins in solution. Problems in the formulation of proteins to be overcome will then become clearer. 

Unlike earlier books in which chemical stability profiles and the effects offactors such as pH and other catalytic contributions on single substances were described extensively, the present text attempts to take a more global approach. Specifically, analysis of the factors affecting drag stability based on basic kinetic theory allowed for a sound theoretical treatment of available information. Furthermore, the bases for physical degradation kinetics, which have generally been treated empirically, are also covered, and sound bases for the observations are also presented and discussed. 

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