Instability aggregation

Figure 10.1 Colloidal dispersions are Inherently unstable systems and in the long run the attractive forces will dominate and the colloidal system will destabilize. However, colloid stability depends on the attractive van der Waals and the repulsive electrical or steric (polymeric) forces. The repulsive forces stabilize a dispersion if they are larger than the van der Waals (vdW) ones (and the total potential is larger than the "natural" kinetic energy of the particles). Surfaces are Inherently unstable and the van der Waals forces "take the system" back to its stable (minimum surface area) condition and contribute to instability (aggregation)...

There are both similarities and differences between interparticle and intermoleculai potential functions. The most important difference is, possibly, that interparticle forces are much more long-range than those between molecules. Let us recall the most important characteristics of this plot the vdW attractive forces (negative V) which lead to instability (aggregation) and the repulsive electrical forces (positive V), which are due to the fact that the particles are charged, which help flie stability . 

The interaction between the dispersed-phase elements at high volume fractions has an impact on breakup and aggregation, which is not well understood. For example, Elemans et al. (1997) found that when closely spaced stationary threads break by the growth of capillary instabilities, the disturbances on adjacent threads are half a wavelength out of phase (Fig. 43), and the rate of growth of the instability is smaller. Such interaction effects may have practical applications, for example, in the formation of monodisperse emulsions (Mason and Bibette, 1996). 

Content uniformity and long-term stability of a pharmaceutical product are required for a consistent and accurate dosing. Aggregation of dispersed particles and resulting instabilities such as flocculation, sedimentation (in suspensions), or creaming and coalescence (in emulsions) often represent major problems in formulating pharmaceutical disperse systems. 

The problems causing the observed instability of colloids stems from the interface separating the two phases. In French dressing, for example, each oil particle is surrounded with water. The instability of the water-air interface causes the system to minimize the overall area of contact between the two phases, which is most readily achieved by the colloid particles aggregating and thereby forming two distinct phases, i.e. oil floating on water. 

Fig. 3. Solubility of silk proteins in solution as a function of time. Low solubility corresponds to protein aggregation. The fast and slow aggregations are observed in vitro (Dicko et al., 2004a), whereas the stable helical conformation (storage structure) is observed in vivo (Dicko et al., 2004b,d). This illustrates the inherent instability of silk protein in solution and shows the /(-sheet polymorph structure as the most stable form. In other words, the spiders actively control and modulate the unavoidable silk protein aggregation prior to fiber formation.

A shortcoming is the instability against external conditions, in particular temperature. To induce a phase transition with a minimum amount of photochemical change, the molecular aggregate system... 

New nitrosothiols are being synthesized and tested for activity. These include structures 1-6 in Section II.A as well as those derived from cysteine residues within proteins. One example of a S-nitrosocysteine within a polypeptide46 is remarkably stable in the solid form, contrasting with the marked instability of S-nitrosocy stein e itself. The S,S dinitrosodithiol 11 has been shown to have platelet aggregation inhibition properties of the same order of magnitude as GTN and vasodilation properties somewhat less than those possessed by GTN17. 

It is also possible to use microcalorimetry to obtain useful information about the kinetic processes of the instability (i.e., aggregation, proteolysis) when thermal irreversibility prevails. Scan rates will often distort the onset behavior of the melting transition that can necessarily impose a shift in the Tm, as discussed further in the following text. The scan rate dependence of the Tm may then be used to determine the activation energy of the instability, provided an Arrhenius kinetic model describes the behavior. 

It should be noted that the unfolding kinetics can sometimes involve quite complex unfolding schemes of different substates in equilibrium with the native state. Staphylococcal nuclease is an example of such behavior, known to unfold with three different substates that exhibit an equilibrium that does not appear to shift with temperature.49 Irreversible aggregation processes of proteins have been known to involve first- or second-order reactions.132141 The mechanism of recombinant human interferon-y aggregation is an example where thermodynamic and kinetic aspects of the reaction provided a powerful tool for understanding the pathway of instability and permitted a rationale for screening excipients that inhibited the process.141... 

If SLN are incorporated into vehicles, interactions with the vehicle constituents may induce physical instabilities such as dissolution or aggregation of lipid particles. Therefore, during storage, particle sizes and the solid character of the particles have to be followed. 

Several limitations and shortcomings are associated with the use of micelles as the pseudosta-tionary phase. Besides the irreversible incorporation of very hydrophobic compounds within the micelles, other analytes snch as proteins may strongly interact with the free molecules of the surfactant in solntion. Moreover, the significant influence of operational parameters such as temperature, pH, and composition of the BGE on the dynamic aggregation of the surfactant molecules may result in instable micelles and consequent irreproducibility. 

All proteins and peptides display chemical and physical instability that affects the way they are distributed and cleared in the body and their delivery to the site of action. Physical and chemical instability is affected by primary sequences and secondary and tertiary structures and the degree of glyco-sylation of protein. Chemical degradation of proteins and peptides involves deamidation, racemization, hydrolysis, oxidation, beta elimination, and disulfide exchange. Physical degradation of proteins involves denaturation and aggregation. 

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