Chemical and Physical Stability

CyDs accelerate or decelerate various reactions, ediibiting many kinetic features shown by enzyme reactions, i.e. catalyst-substrate complex formation, competitive inhibition, saturation, and stereospecific catalysis [67]. CyD-catalyzed reactions can generally be classified in the following three categories according to the type of stimulation (a) partidpation of the hydroxyl groups of CyDs (b) the microsolvent effect of the hydrophobic CyD cavity and (c) the conformational or steric effect of CyDs [67]. 

Tolbutamide and chlorpropamide are oral hypoglycemic agents with low solubilities and dissolution rates in water. Both drugs have several polymorphic forms (Forms I-IV etc. for tolbutamide and Forms A-C etc. for chlorpropamide). The dissolution rates of the metastable forms of both drugs are higher than those of the stable forms (Form I and Form A for tolbutamide and chlorpropamide, respectively). The metastable Form IV and Form C are obtained by the spray-drying 

Crystallization of tolbutamide from aqueous solution was significantly affected by CyD complexation (Fig. 14.8) [76]. When the supersaturated transparent tolbutamide solution was stored at 4 °C, the stable Form I crystallized exclusively. On the other hand, a solution containing 2 gave only the metastable Form IV of tolbutamide. DM-a-CyD with the smaller cavity gave the stable Form I crystals. Detailed investigation indicated that crystallization of tolbutamide proceeds via the metastable Form IV, which quickly converts to the stable Form I within 15 h at 4 °C. However, conversion of Form IV to Form I in 2 solutions was markedly suppressed, and continued for at least three more days. This suppression is attributable to inclusion complexation of tolbutamide with 2, because the addition of competitive inhibitors gave the stable Form I crystals. 2 seems to be effective in suppressing conversion of the metastable form to the stable form in the solution. 

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Chemical and physical stability (degradation, aggregation or fusion, reduction of drug retention)... 

Where the instructions for use of the product involve admixture or dilution with drinks or other materials, appropriate compatibility data will be required. Factors to consider include ease and rate of dissolution, homogeneity, chemical and physical stability over the period of use, particle size, etc. 

Chemical and physical stability => to assure long lifetime of the PCM. 

The chemical and physical stability of a solid drug decreases with decreasing crystallinity and increasing amorphous character, corresponding to an increase in molecular mobility (i.e., diffusivity) in the solid state. This phenomenon is of particular significance to proteins, peptides, and other biological materials. Certain additives other than water may stabilize proteins in the solid state, perhaps by locking in the defects. 

The chemical and physical stability of aqueous and nonaqueous suspensions of a number of solvatomorphs of niclosamide has been evaluated in an effort to develop pharmaceutically acceptable suspension formulations [90]. Studied in this work was the anhydrate, two polymorphic monohydrates, the 1 1, Y, A"-dimethyI I ormam ide solvatomorph, the 1 1 dimethyl sulfoxide solvatomorph, the 1 1 methanol solvato-morph, and the 2 1 tetraethylene glycol hemisolvate. All of the solvatomorphs were found to convert initially to one of the polymorphic monohydrates, and over time converted to the more stable monohydrate phase. The various solvatomorphs could be readily desolvated into isomorphic desolvates, but these were unstable and became re-hydrated or re-solvated upon exposure to the appropriate solvent. 

The parent 1,2,4-triazole has been investigated as a potential reference compound for use in combustion experiments of compounds that contain nitrogen atoms using a micro-bomb calorimetry experiment. Urea was used previously as a standard but the chemical and physical stability of 1,2,4-triazole lends itself to such a role <2000MI949>. 

Traditionally, ultrafilters have been manufactured from cellulose acetate or cellulose nitrate. Several other materials, such as polyvinyl chloride and polycarbonate, are now also used in membrane manufacture. Such plastic-type membranes exhibit enhanced chemical and physical stability when compared with cellulose-based ultrafiltration membranes. An important prerequisite in manufacturing ultrafilters is that the material utilized exhibits low protein adsorptive properties. 

Polymorphism is critically important in the design of new drug API [9] and affects a number of areas. The main impact is to the bioavailability and release profile of a drug substance into the body. This is due to differences in solubility and dissolution rate, between the polymorphs. The chemical and physical stability of the formulated drug substance is also dependent on the polymorphic form. Patented registration of all discovered forms and their manufacturing conditions is an important element in protecting a pharmaceutical companies intellectual property. 

Paboiji, M., N.L. Pochopin, W.P. Coppola, and J.B. Bogardus (1994). Chemical and physical stability of chimeric L6, a mouse-human monoclonal antibody. Pharm Res 11(5) 764-771. 

The utility of polymer-supported phase transfer catalysts depends upon their ease of synthesis and their chemical and physical stability. The advantages of the heterogeneous catalysts are the ease of separation of the catalyst from reaction mixtures and reuse. Although there may occasionally be cases of higher activity of heterogeneous... 

The chief interest of petroleum chemists in the information presented here may be in the fact that, although the earlier kerosene type of petroleum derivatives mixture will produce insecticide fogs—and is still used successfully for them—an analysis of fog production and its use, from biological, physical, chemical, and mechanical standpoints, has resulted in the evolution of special fog oils which combine higher DDT solvency, specific insecticidal potency, greater safety, and greater chemical and physical stability with consequent limited and therefore more desirable particle size range, at known temperatures and pressures. 

Proteins, peptides, and other polymeric macromolecules display varying degrees of chemical and physical stability. The degree of stability of these macromolecules influence the way they are manufactured, distributed, and administered. Chemical stability refers to how readily the molecule can undergo chemical reactions that modify specific amino-acid residues, the building blocks of the proteins and peptides. Chemical instability mechanisms of proteins and peptides include hydrolysis, deamidation, racemization, beta-elimination, disulfide exchange, and oxidation. Physical stability refers to how readily the molecule loses its tertiary and/or sec-... 

The polymerization of bilayers is usually associated with the chemical and physical stabilization of the bilayer membranes. The polymerization of mono-... 

Refractories. Its low coefficient of expansion, high thermal conductivity, and general chemical and physical stability make silicon carbide a valuable material for refractory use. Suitable applications for silicon carbide refractory shapes include boiler furnace walls, checker bricks, mufflers, kiln furniture, furnace skid rails, trays for zinc purification plants, etc (see REFRACTORIES). 

The effects involved, from an optical point of view, are an increase of reflectivity, and both opacity and anisotropy. These effects, and others—e.g., insolubility or microhardness—appear to be related to an increase in chemical and physical stability. If one considers that these effects are stable towards further geological agents, we now realize that we have in hand a "geological photographic plate/ This optimistic approach should not hide the fact that data and information obtained are rather complex and that our understanding of the basic phenomena is still inadequate. We shall thus confine ourselves to describing and interpreting a few typical examples. 

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). 

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