Physical stability solutions

Bindschaedler and Gurny [12] published an adaptation of the simplex technique to a TI-59 calculator and applied it successfully to a direct compression tablet of acetaminophen (paracetamol). Janeczek [13] applied the approach to a liquid system (a pharmaceutical solution) and was able to optimize physical stability. In a later article, again related to analytical techniques, Deming points out that when complete knowledge of the response is not initially available, the simplex method is probably the most appropriate type [14]. Although not presented here, there are sets of rules for the selection of the sequential vertices in the procedure, and the reader planning to carry out this type of procedure should consult appropriate references. 

Chi, E.Y., Krishnan, S., Randolph, T.W., and Carpenter, J.F. 2003. Physical stability of proteins in aqueous solution mechanism and driving forces in nonnative protein aggregation. Pharmaceutical Research 20(9), 1325-1336. 

In general the preparation of a polymer monolithic rod is performed as a multi-step procedure (Figure 11). Generally, the stages involved are pre-treatment and preparation of the monolithic matrix by polymerization and derivatization or functionalization. Pre-treatment of the bare capillary is sometimes needed in order to obtain good physical stability. Most columns are therefore polymerized in silanized columns. The capillary column is first washed with a strong alkaline solution such as 1.0 M sodium hydroxide so that the siloxane groups at... 

Kendrick BS, Li T, Chang BS. Physical stabilization of proteins in aqueous solution. In Carpenter JF, Manning MC, eds. Rational Design of Stable Protein Formulations Theory and Practice. Pharmaceut Biotechnol 2002 13 61-84. 

Chemical Stability. Chemical stability is just as important as the physical stability just discussed. In general, chemical deterioration of the polymers is no problem, and they can be stored at room temperature for years. However, the polymeric surfaces are subjected to an extreme variety of chemicals during the accumulation process. Some of these may react with the polymer. For example, reactions of styrene-divinylbenzene polymers and Tenax with the components of air and stack gases have been documented (336, 344, 540). The uptake of residual chlorine from water solutions has also been observed in my laboratory and elsewhere (110, 271, 287). Although the homogeneous nature of synthetic polymers should tend to reduce the number of these reactions relative to those that occur on heterogeneous surfaces of activated carbons, the chemical reaction possibility is real. In the development of methods for specific chemicals, the polymer stability should always be checked. On occasion, these checks may lead to... 

The physical stability of the casein micelle system is closely related to the degree of lactose crystallization from the unfrozen phase of the frozen concentrate. Crystallization of lactose from the unfrozen solution temporarily raises its freezing point, causing additional water to freeze, thus increasing the concentration and promoting destabilization of casein micelles. 

Water activity (aw) is the ratio of the partial vapor pressure of water above a solution to that of pure water at the same specific temperature. It plays an important role in evaluating the microbial, chemical, and physical stability of foods during storage and processing. The vapor pressure in the headspace of a food sample can be measured directly by a manometer. A manometer has one or two transparent tubes and two liquid surfaces where pressure applied to the surface of one tube causes an elevation of the liquid surface in the other tube. The amount of elevation is read from a scale that is usually calibrated to read directly in pressure units. Makower and Myers (1943) were the first to use this method to measure vapor pressure exerted by food. Later, the method was improved, in terms of design features of the apparatus, by various scientists (Taylor, 1961 Labuza et al., 1972 Lewicki, 1987). Trailer (1983), Lewicki (1989), and Zanoni et al. (1999) used a capacitance manometer instead of a U-tube manometer for the measurement of vapor pressure. Lewicki et al. (1978) showed that the precision and reproducibility of the method can be improved by the simultaneous measurement of the water vapor pressure and temperature of the food sample. The method is reviewed in detail by Rizvi (1995) and Rahman (1995). 

Physical Stability. Physical stability depends primarily on the purity of the enzyme. Impurities remaining from the fermentation broth may precipitate or form a hazy solution. Unwanted sedimentation is often related to Ca2+ or acidic polysaccharides. The solubility of some enzymes can be increased by optimizing the ionic strength or changing the dielectric constant of the solution by adding low molecular-weight polyols. 

Chemical modification of electrode surfaces by polymer films offers the advantages of inherent chemical and physical stability, incorporation of large numbers of electroactive sites, and relatively facile electron transport across the film. Since th% polymer films usually contain the equivalent of one to more than 10 monolayers of electroactive sites, the resulting electrochemical responses are generally larger and thus more easily observed than those of immobilized monomolecular layers. Also, the concentration of sites in the film can be as high as 5 mol/L and may influence the reactivity of the sites because their solvent and ionic environments differ considerably from dilute homogeneous solutions [9]. 

The problem with using surfactant-modified stationary phases in LC is that the surfactant will usually slowly elute (bleed) from the support thus resulting in different retention behavior of solutes with time. This is why most applications are in the area of GC or GLC. An exciting recent advance has been reported by Okahata, et al (181). Namely, a procedure has been developed for immobilizing a stable surfactant vesicle bilayer as the stationary phase in GC. A bilayer polyion complex composed of DODAB vesicles and sodium poly(styrene sulfonate) was deposited on Uniport HP and its properties as a GC stationary phase evaluated. Unlike previous lipid bilayers which exhibited poor physical stability, the DODAB polyion phase was stable. Additionally, the temperature-retention behavior of test solutes exhibited a phase transition inflection point. The work demonstrates that immobilized surfactant vesicle bilayer stationary phases can be employed in GC separations (181). Further work in this direction will likely lead to many such unique gas chromatographic supports and novel separations. 

Simple determination of physical stability, i.e., are there particles in solution, is the solution the correct color/turbidity Is the container closure system seemingly intact ... 

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