Amorphous systems stability

Perspectives for fabrication of improved oxygen electrodes at a low cost have been offered by non-noble, transition metal catalysts, although their intrinsic catalytic activity and stability are lower in comparison with those of Pt and Pt-alloys. The vast majority of these materials comprise (1) macrocyclic metal transition complexes of the N4-type having Fe or Co as the central metal ion, i.e., porphyrins, phthalocyanines, and tetraazaannulenes [6-8] (2) transition metal carbides, nitrides, and oxides (e.g., FeCjc, TaOjcNy, MnOx) and (3) transition metal chalcogenide cluster compounds based on Chevrel phases, and Ru-based cluster/amorphous systems that contain chalcogen elements, mostly selenium. 

Using Differential Scanning Calorimetric and Roentgen-phase analyses methods it has been established that synthesized polymers are amorphous systems. Thermal (phase) transformation temperatures of synthesized polymers have been determined. Thermooxidation stability of the synthesized polymers has been studied. There was shown that their thermooxidation stability exceeded the analogical characteristic of polyorganocarbosiloxanes. 

With nonionic PEO emulsifiers, intermolecular interactions vary with temperature and types of metal ions and solvents. At low temperatures, nonionic emulsifiers are hydrophilic and form normal micelles. At higher temperatures they are lipophilic and form reverse micelles. A weak interaction with metal ions favors the stability of associates against moisture. On the other hand, a strong interaction may lead to a completely amorphous system. Ethanol as a co-solvent is a moderate solvent for PEO at low temperatures, but its power improves as the temperature is raised [34]. This means that solutions of the PEO copolymers in water and ethanol have opposing temperature coefficients of solubility negative for water and positive for ethanol. 

In addition to characterizing frozen systems intended to be freeze dried, it is important to characterize the freeze-dried product. This includes determination of the physical state of the dried product that is, crystalline, partially crystalline, or amorphous. It may also include identification of the polymorph of a crystallizing component which exhibits polymorphism and determination of whether the crystal form observed is affected by changes in formulation and processing conditions. For amorphous systems, the glass transition temperature of the amorphous solid, as well as the extent to which Ts changes with residual moisture, may be a critical attribute of the product with regard to both physical and chemical stability. 

Before proceeding further, it is appropriate to discuss some aspects of molecular mobility of amorphous solids as it affects stability. The temperature dependence of molecular motion in amorphous systems is described by the empirical Vogel-Tammann-Fulcher (VTF) equation ... 

X-ray diffraction analysis indicates that oligomers are amorphous systems with the interchain dis-tance equal d 8.64 A. Thermogravimetric studies show that by thermal oxidative stability oligo-mers are behind polyorganocyclotetrasiloxanes only. 

In amorphous systems, e.g. in rubbers, a better solubility of stabilizers and a more uniform distribution than in polyolefins can be reached. The equilibrium stabilizer concentration should not exceed the saturation state to prevent stabilizer blooming after 1 year storage at ambient temperature. Complications may arise with insoluble stabilizers, as with JV,h/ -diaryl-l,4-phenylenediamine in rubbers [16]. The limited solubility does not allow a sufficient antiozonant protection to be achieved. 

If data were available for the free energy and/or kinetics of unfolding in amorphous systems of direct relevance to freeze-drying, the question of stabilization mechanism could perhaps be resolved. Unfortunately, these data are not... 

The crystallization process often follows the mechanism of three-dimensional growth of nuclei after an induction period. Amorphous forms of the same compound made by different methods can have different physical stabilities due to kinetic differences of the crystal nucleation and growth processes [31]. When evaluating the physical stability of amorphous systems, the properties of the crystalline counterpart should also be considered regarding the enthalpic driving force for crystallization and activation energy for nucleation [32]. 

Gupta, P ThUagavathi, R. Chakraborti, A.K. Bansal, A.K. Role of molecular interaction in stability of celecoxib-PVP amorphous systems. Mol. Pharm. 2005, 2(5), 384-391. 

Chemical and aggregation stability of hGH in several other 100% amorphous systems are compared with corresponding stability in pure protein and the glycine mannitol formulation in Figure 5 [38]. Hydroxyethyl starch (HES), stachyose, and trehalose are formulated in a 1 1 weight ratio of excipient hGH, whereas the dextran formulation is 6 1 dextran hGH. While the concept that an excipient system must remain at least partially amorphous to improve protein stability is not in question, it is clear that... 

Calculation of the thermodynamic quantities requires the system under investigation to be in equilibrium. For an amorphous system, this is achieved in the temperature range above the Tg, in the supercooled liquid state. Theoretically, the calculations of the configuration thermodynamic properties are not valid for the glass however, the behavior of the amorphous form above the Tg may give an indication on the stability behavior below the Tg and calculation of these parameters provides further information on the behavior of the amorphous form. 

Graeser KA, Patterson JE, Zeitler JA, Gordon KC, Rades T (2009b) Correlating thermodynamic and kinetic parameters with amorphous stability. Eur J Pharm Sci 37(3-4) 492-498 Graeser KA, Patterson JE, Zeitler JA, Rades T (2010) The role of configurational entropy in amorphous systems. Pharmaceutics 2 224-244... 

Wyttenbach N, Janas C, Siam M, Lauer ME, Jacob L, Scheubel E, Page S (2013) Miniaturized screening of polymers for amorphous drug stabilization (SPADS) rapid assessment of solid dispersion systems. Eur J Pharm Biopharm 84(3) 583-598... 

Yoo SU, KriU SL, Wang Z, Telang C (2009) MiscibiUty/stability considerations in binary solid dispersion systems composed of functional excipients towards the design of multi-component amorphous systems. J Pharm Sci 98(12) 4711-4723... 

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