Compound dissolution

The effect of polymorphism becomes especially critical on solubility since the rate of compound dissolution must also be dictated by the balance of attractive and disruptive forces existing at the crystal-solvent interface. A solid having a higher lattice free energy (i.e., a less stable polymorph) will tend to dissolve faster, since the release of a higher amount of stored lattice free energy will... 

Rohrs BR. Dissolution method development for poorly soluble compounds. Dissolution Technol 2001 8(3) 6—12. 

Dissolution of a drug substance is controlled by several physicochemical properties, including solubility, surface area, and wetting properties. For insoluble compounds, dissolution is often the rate-limiting step in the absorption process. Knowledge ofthe dissolution rate of a drug substance is therefore very useful for formulation development. The appropriate dissolution experiments can help to identify factors that contribute to bioavailability problems, and also assist in the selection of the appropriate crystal form and/or salt form. Dissolution tests are also used for other purposes such as quality control and assisting with the determination of bioequivalence (Dressman et al., 1998). 

For highly water-soluble compounds, dissolution and absorption usually are complete within a few hours or less (given that permeability is adequate). For compounds with short half-lives, repeated dosing may be required to maintain in vivo drug concentrations within therapeutical levels. In these cases, extended release dosage forms are suitable to overcome the frequent dosing problem, leading to better patient compliance. 

Currently, most mature dissolution controlled release systems/ technologies are applicable for water-soluble and low-water-solubility compounds (with low doses). For very poorly water-soluble compounds, dissolution controlled release systems/technologies may not be applicable because these compounds have intrinsically slow dissolution/release rates. Recently, several new technologies such as solid dispersions and self-emulsifying drug delivery systems (SEDDS) have been developed to deliver poorly water-soluble compounds at reasonable doses through enhancement of dissolution rate. These technologies have created new potentials for controlled release of poorly water-soluble compounds, often... 

Any aqueous waste, such as dissolution media, that is generated should also be evaluated on a case-by-case basis. Potent compounds are normally dosed in formulations containing milligram or lower levels of active compound. Dissolution or other aqueous wastes are therefore normally very dilute solutions. As long as there are no ecological toxicity issues, dissolution media and aqueous wastes containing potent compounds can normally be incorporated into the standard aqueous waste stream. If there are any toxicity issues associated with the wastes, the aqueous wastes and dissolution media should be segregated from the normal waste stream and treated in an appropriate manner. 

High throughput in-well sonication has been applied to dissolve compounds that are insoluble in DMSO in 96, 384, and 1536 well formats (Oldenburg et ah, 2005). Compounds that precipitated from DMSO stocks, due to either water uptake that reduced solubility or low instrinsic solubility that promoted crystallization, can be re-dissolved by low energ) sonication. Sonication can accelerate compound dissolution in seconds and, in some cases, drive the solution to super saturation, due to energy input and elevated temperature. This process can bring many precipitates back into solution and has no effect on compound stability. Sonication of DMSO stocks or concentrated aqueous solutions can improve HTS hit rates and enhance biological assay results. 

Optical properties of a photoresist are determined by its base polymer as well as additives in the photoresist system, such as photoactive compounds, dissolution inhibitors, etc. Tables 57.6 and 57.7 list optical properties of some commercial 1-line (365 nm) and DUV (248 nm) resists. 

Contact time, temperature and sulfiting are factors that influence phenolic compound dissolution and color in rose wines (Castino, 1988). Sulfur dioxide is known to have a certain dissolvent power (Section 8.7.5). It is not manifested during traditional red winemaking, due to the preponderant effects of other factors (duration, temperature and pumping-over). Yet when maceration is limited, the effect of sulfiting is obvious. Table 14.3 shows the impact of the winemaking techniqne on the color intensity and phenolic componnd concentrations of rose wines. Sulfiting promotes anthocyanin dissolution and color enhancement. It is not easy to control the conditions that will produce the required color and phenolic structure, as they depend on the specific characteristics of the wine. 

Metals in higher oxidation states form halides which are essentially covalent, for example AICI3, SnCl, FeClj when these compounds dissolve in water they do so by a strongly exothermic process. Indeed it is perhaps incorrect to think of this only as a dissolution process, since it is more like a chemical reaction—but to differentiate for a particular substance is not easy, as we shall see. The steps involved in the case of aluminium chloride can be represented as... 

The following mechanism of the Sandmeyer reaction has been proposed as a result of a kinetic study, and incidentally accounts for the formation of the azu compounds as by-products. The catalyst is the CuCl ion produced in the dissolution of cuprous chloride in the chloride solution ... 

Compounds which dissolve in concentrated sulphuric acid may be further subdivided into those which are soluble in syrupy phosphoric acid (A) and those which are insoluble in this solvent (B) in general, dissolution takes place without the production of appreciable heat or colour. Those in class A include alcohols, esters, aldehydes, methyl ketones and cyclic ketones provided that they contain less than nine carbon atoms. The solubility limit is somewhat lower than this for ethers thus re-propyl ether dissolves in 85 per cent, phosphoric acid but re-butyl ether and anisole do not. Ethyl benzoate and ethyl malonate are insoluble. 

Group V. This group includes all the water-insoluble hydrocarbons and oxygen compounds that do not contain N or S and are soluble in cold concentrated sulphuric acid. Any changes—colour, excessive charring, evolution of gases or heat, polymerisation and precipitation of an insoluble compound— attending the dissolution of the substance should be carefully noted. 

Kinetic measurements were performed employii UV-vis spectroscopy (Perkin Elmer "K2, X5 or 12 spectrophotometer) using quartz cuvettes of 1 cm pathlength at 25 0.1 C. Second-order rate constants of the reaction of methyl vinyl ketone (4.8) with cyclopentadiene (4.6) were determined from the pseudo-first-order rate constants obtained by followirg the absorption of 4.6 at 253-260 nm in the presence of an excess of 4.8. Typical concentrations were [4.8] = 18 mM and [4.6] = 0.1 mM. In order to ensure rapid dissolution of 4.6, this compound was added from a stock solution of 5.0 )j1 in 2.00 g of 1-propanol. In order to prevent evaporation of the extremely volatile 4.6, the cuvettes were filled almost completely and sealed carefully. The water used for the experiments with MeReOj was degassed by purging with argon for 0.5 hours prior to the measurements. All rate constants were reproducible to within 3%. 

The overall extraction process is sometimes subdivided into two general categories according to the main mechanisms responsible for the dissolution stage (/) those operations that occur because of the solubiHty of the solute in or its miscibility with the solvent, eg, oilseed extraction, and (2) extractions where the solvent must react with a constituent of the soHd material in order to produce a compound soluble in the solvent, eg, the extraction of metals from metalliferous ores. In the former case the rate of extraction is most likely to be controUed by diffusion phenomena, but in the latter the kinetics of the reaction producing the solute may play a dominant role. 

The formation of such materials may be monitored by several techniques. One of the most useful methods is and C-nmr spectroscopy where stable complexes in solution may give rise to characteristic shifts of signals relative to the uncomplexed species (43). Solution nmr spectroscopy has also been used to detect the presence of soHd inclusion compound (after dissolution) and to determine composition (host guest ratio) of the material. Infrared spectroscopy (126) and combustion analysis are further methods to study inclusion formation. For general screening purposes of soHd inclusion stmctures, the x-ray powder diffraction method is suitable (123). However, if detailed stmctures are requited, the single crystal x-ray diffraction method (127) has to be used. 

Acetates. Anhydrous iron(II) acetate [3094-87-9J, Ee(C2H202)2, can be prepared by dissolving iron scraps or turnings in anhydrous acetic acid ( 2% acetic anhydride) under an inert atmosphere. It is a colorless compound that can be recrystaUized from water to afford hydrated species. Iron(II) acetate is used in the preparation of dark shades of inks (qv) and dyes and is used as a mordant in dyeing (see Dyes and dye intermediates). An iron acetate salt [2140-52-5] that is a mixture of indefinite proportions of iron(II) and iron(III) can be obtained by concentration of the black Hquors obtained by dissolution of scrap iron in acetic acid. It is used as a catalyst of acetylation and carbonylation reactions. 

Mercuric Nitrate. Mercuric nitrate [10045-94-0] Hg(N02)2, is a colorless dehquescent crystalline compound prepared by the exothermic dissolution of mercury in hot, concentrated nitric acid. The reaction is complete when a cloud of mercurous chloride is not formed when the solution is treated with sodium chloride solution. The product crystallizes upon cooling. Mercuric nitrate is used in organic synthesis as the starting material and for the formulation of a great many other mercuric products. 

On dissolution in water, peroxohydrates Hberate hydrogen peroxide into solution. Some peroxo salts also Hberate hydrogen peroxide when dissolved in water, and before the introduction of x-ray crystallography, compounds within these classes were often confused with each other. 

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