Solubility characteristic

The solubility of atorvastatin calcium, Form-I, was measured in a variety of solvents (Table 1.2) by taking an excess of atorvastatin calcium in screw-capped vials with 10 ml of the solvent, followed by analysis of the dissolved fraction after 24 h by high-performance liquid chromatography (HPLC). The pH of a saturated solution of atorvastatin calcium in water was found to be 7.12 (Fig. 1.16). 

The predicted value of aqueous solubility using the ACD/I-Lab Web service (ACD/aqueous solubility 8.02) was 20 mg/ml at pH 7.12, which, however, was practically obtained to be 0.8 mg/ml. 

TABLE 1.2 Solubility of atorvastatin calcium in different solvents  

FIGURE 1.16 pH-Solubility profile of atorvastatin calcium, as predicted using the advanced chemistry development program. 

Determination of the solubility characteristics of an organic compound can often give valuable information as to its structural composition. It is especially useful when correlated with spectral analysis. Several schemes have been proposed that place a substance in a definite group according to its solubility in various solvents. The scheme presented below is similar to that outlined in Shriner et al.  

There is no sharp dividing line between soluble and insoluble, and an arbitrary ratio of solute to solvent must be selected. We suggest that a compound be classified as soluble if its solubility is greater than 15 mg/500 (xL of solvent. 

Carry out the solubility determinations, at ambient temperature, in 10 X 75-mm test tubes. Place the sample (—15 mg) in the test tube and add a total of 0.5 mL of solvent in three portions from a graduated or calibrated Pasteur pipet. Between addition of each portion, stir the sample vigorously with a glass stirring rod for 1.5-2 min. If the sample is water soluble, test the solution with litmus paper to assist in classification according to the solubility scheme that follows. 

To test with litmus paper, dip the end of a small glass rod into the solution and then gently touch the litmus paper with the rod. Do not dip the litmus paper into the test solution. 

In doing the solubility tests follow the scheme in the order given. Keep a record of your observations. 

The synthesis of these polymers is the subject of another chapter and thus details will not be reviewed here. However, it is important to understand some of the differences in structure to be able to understand the properties of these polymers in solution. The block systems consisted of anionically polymerized styrene and tert-butyl styrene blocks [7]. The styrene units were sulfonated and following neutralization with base, the polymers were rendered water soluble. These polymers rely on ionic functionality for water solubility. The hydrophobic unit is a chain of tert-hutyl styrene groups and thus is quite bulky. 

The two random architectures are derived from free radical polymerization of acrylamide with either an alkylacrylamide [5] or a nonylphenoxy-poly(etheroxy) acrylate monomer [6, 13]. Type (1) systems require the micellar polymerization to enable incorporation of the hydrophobic monomer. The backbones of these polymers are built from nonionic, water-soluble monomers and thus are quite different than the type (3) block copolymers in terms of solubility characteristics. 

Solubility characteristics of high molecular weight polymers can be problematic. Long dissolution times and fish eyes in the final solution are often observed. Associating polymers have additional complexity. The solution history of the polymer can affect inter- and intramolecular associations which influence dissolution rates. Preparing solutions above the polymer overlap concentration, C, requires patience and care. The design of the polymer structure can greatly affect solubility and dissolution characteristics. 

The solubility characteristics of hydrophobically associating copolymers of p(alkyl acrylamide-co-acrylamide), RAM, have been studied by a number of 

Another way to improve the solubility characteristics of hydrophobically associating polymers is through incorporation of water-soluble, ionic monomers into the polymer. Carboxylate functionality has been introduced into RAM polymers by either copolymerization with acrylic acid salt or by a postpolymerization partial hydrolysis of the acrylamide groups. Incorporating about 20 mol% sodium acrylate functionality, significantly improves solubility of these HRAM polymers. Sulfonate groups can be introduced by copolymerizing with a sulfonate monomer such as vinyl sulphonate or 2-acrylamido-2-methylpropane sulfonate, AMPS. We call these polymers SRAM. 

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Maleic acid and fumaric acid can also be, and are often, incorporated in alkyd resins in the form of the Diels-Alder adduct of rosin. The adducts are tribasic acids which provide pendent carboxyl groups in the resin molecules, which can be saponified to give ionic, and, in turn, water-soluble characteristics to the resin. However, the resultant alkyds often have poorer color retention, toughness, gloss retention, and exterior durabiUty. 

Potassium Heptafluorotantalate. Potassium heptafluoiotantalate [16924-00-8], K TaF, ciystallizes in colodess, rhombic needles. It hydroly2es in Foiling water containing no excess of hydrofluoric acid. The solubility of potassium heptafluorotantalate in hydrofluoric acid decreases from 60 g/100 mL at 100°C to 0.5 g/100 mL at room temperature. The different solubility characteristics of K TaF and K NbOF are the fundamental basis of the Matignac process (16). A phase diagram exists for the system K TaF —NaCl—NaF—KCl (68). Potassium heptafluorotantalate has an LD q value of 2500 mg/kg. The recommended TWA maximum work lace exposure for K TaF in air is 2.5 mg /m (fluoride base) (69). 

In the course of developing the Polacolor and SX-70 processes many insulated dye developers were synthesized and investigated. An extensive review of this work is available (21). The insulating linkage, chromophore, and developer moiety can each be varied. Substituents on the developer modify development and solubility characteristics substituents on the chromophore modify the spectral characteristics in terms of both color and tight stability. The attachment of two dyes to a single developer by amide linkage has also been described (22). 

No detailed study of the solubility characteristics of more complexly substituted isoxazoles has been made. However, qualitative indications of solubility characteristics may be found associated with their synthesis. 

The use of potassium hydroxide rather than sodium hydroxide is dietated by solubility characteristics which make purification of the sodium alkoxide difficult. 

TTie relationship between degree of substitution and solubility characteristics is predictable from theory and is summarised in Table 22.5. 

The cyanohydrin of methyl perfluoroheptyl ketone was synthesized by a two-step process addition of sodium bisulfite and subsequent treatment with sodium cyanide. When the ketone was reacted with sodium cyanide, cyclic addition products were obtained, instead of the product of cyanohydrin formation. This result was attributed to the solubility characteristic of a long perfluoroalkyl group, which makes the compound less soluble in water and polar organic solvents [54] (equation 40) (Table 14). 

This derivative was used to improve the solubility characteristic of an argininal semicarbazone for solution-phase peptide synthesis. 

Dissolution of 5 could be enhanced in H2O by solid dispersion systems with urea and mannitol (97MI27). A method for solubilizing 5 and 6 at near physiological pH was patented (98EUP856316). Solubility characteristics of 5 was investigated in an in vitro tear model (98MI24). 

Besides the shortcomings noted above, some of the early sulfa drugs were poorly soluble in water. Since the drugs are excreted largely unchanged in the urine, crystals of the compounds sometimes formed in the kidneys and urine with attendant discomfort and tissue damage. Considerable attention was therefore devoted to preparation of agents with better solubility characteristics. ... 

Tunability of the solubility characteristics of the ionic liquids Solvent effect... 

Notwithstanding their very low vapor pressure, their good thermal stability (for thermal decomposition temperatures of several ionic liquids, see [11, 12]) and their wide operating range, the key property of ionic liquids is the potential to tune their physical and chemical properties by variation of the nature of the anions and cations. An illustration of their versatility is given by their exceptional solubility characteristics, which make them good candidates for multiphasic reactions (see Section 5.3.4). Their miscibility with water, for example, depends not only on the hydrophobicity of the cation, but also on the nature of the anion and on the temperature. 

The influence of the nature of cations and anions on the solubility characteristics of the resulting salts with organic substrates is also discussed in Section 5.3.4. It has... 

One of the key factors controlling the reaction rate in multiphasic processes (for reactions talcing place in the bulk catalyst phase) is the reactant solubility in the catalyst phase. Thanks to their tunable solubility characteristics, the use of ionic liquids as catalyst solvents can be a solution to the extension of aqueous two-phase catalysis to organic substrates presenting a lack of solubility in water, and also to moisture-sensitive reactants and catalysts. With the different examples presented below, we show how ionic liquids can have advantageous effects on reaction rate and on the selectivity of homogeneous catalyzed reactions. 

In comparison with classical processes involving thermal separation, biphasic techniques offer simplified process schemes and no thermal stress for the organometal-lic catalyst. The concept requires that the catalyst and the product phases separate rapidly, to achieve a practical approach to the recovery and recycling of the catalyst. Thanks to their tunable solubility characteristics, ionic liquids have proven to be good candidates for multiphasic techniques. They extend the applications of aqueous biphasic systems to a broader range of organic hydrophobic substrates and water-sensitive catalysts [48-50]. 

Its solubility characteristics in aqueous systems are such that retention of toxicity to insects by dissolved crystal protein is always suspect, and loss of activity on dissolution owing to denaturation is often observed. The protein is soluble only in relatively strong aqueous alkali. Thus, it has been variously reported to be soluble in 0.01N- to 0.05N sodium hydroxide (1) and alkali at pH 10.5 in the presence of thioglycollate (35) we have also observed its solubility in alkali at pH 9.5 in the presence of urea and potassium boro hydride. One difference between the characteristic proteins produced by various strains of crystalliferous bacilli is observed in the degree of alka-... 

The color of the derivative alkylbenzenesulfonic acid is clearly better. The solubility characteristics remain good. An olefin from the Pacol-Olex process (C, 0/13 olefin) is used as a starting olefin. The DeFine step is employed to reduce the diolefin content to <0.5%. With such an olefin an LAB is obtained over an aluminum chloride catalyst with a linear content of >99% and from which the sulfonation product has a biodegradability (DOC) comparable to that of other LABs[122,123].Table 25 gives typical physical-chemical data about different LAB types. 

Because of its superior solubility characteristics, a high 2-phenyl LAS (with an alkyl chain length average of 11.4) was the preferred type. The detergency performance of one LAS/AE type of formulation was discussed previously (see Figs. 12 and 13). Early commercial heavy-duty liquid (HDL) formulations were built with phosphate, but since 1979 almost all U.S. HDLs have been formulated without phosphate. 

Although each of these cyclic siloxane monomers can be polymerized separately to synthesize the respective homopolymers, in practice they are primarily used to modify and further improve some specific properties of polydimethylsiloxanes. The properties that can be changed or modified by the variations in the siloxane backbone include the low temperature flexibility (glass transition temperature, crystallization and melting behavior), thermal, oxidation, and radiation stability, solubility characteristics and chemical reactivity. Table 9 summarizes the effect of various substituents on the physical properties of resulting siloxane homopolymers. The... 

The most commonly used siloxane modifiers are those having phenyl, trifluoro-propyl and cyanopropyl substituents. Introduction of phenyl units into the polydimethylsiloxane backbone either in the form of methylphenylsiloxane or diphenyl-siloxane increases the thermal and oxidative stability, glass transition temperature and the organic solubility characteristics of the resulting copolymers. At low levels (5-10 percent by weight) of incorporation, bulky phenyl groups also break up the regularity of polydimethylsiloxane chains and inhibit the crystallization (Tc... 

Detailed information on the copolymerization of cyclic trifluoropropylmethyl-siloxane trimer and octamethylcyclotetrasiloxane is also very limited in the open literature26 27 . Recently, preparation of various amine terminated (dimethyl-tri-fluoropropyl,methyl)siloxane oligomers with varying molecular weights and backbone compositions has been reported 69115 ll7). Table 11 shows various properties of the oligomers produced as a function of composition. These types of modification play very important roles in determining the solubility characteristics and hence the compatibility of resultant polysiloxanes with other conventional organic monomers... 

As described in Chapter H, there are four different kinds of solids network, molecular, metallic, and ionic. Each is held together by a different kind of interaction, so each has its own solubility characteristics. 

C21-0059. Prepare a list of the industrial reactions described In Section 21-1 that use sulfuric acid because of sulfate solubility characteristics. 

That dendrimers are unique when compared with other architectures is confirmed by an investigation on porphyrin core dendrimers and their isomeric linear analogues [63]. The isomers displayed dramatically different hydrodynamic properties, crystallinity, and solubility characteristics when compared to those of their dendritic analogues, and photophysical studies showed that energy transfer from the poly(benzylether) backbone to the core was more efficient in the dendrimer because of the shorter distance between the donor units and the acceptor core. 

Since a-tocopherol destroys nitrite in the system in absence of the oil phase, we may postulate that the ineffectiveness of these two oil soluble inhibitors resulted from their absence from the aqueous phase. Diethanolamine is miscible with water and presumably its nitrosation occurs in the aqueous phase. There is a significant difference in the solubility characteristics of ascorbyl palmitate. The reducing portion of the molecule is water soluble. Thus the ascorbate moiety may be in the aqueous phase while the fatty acid tails may lie within the oil globules. The a-tocopherol and the BHA may well be effective if they are dispersed in the aqueous phase after preparation of the emulsion. This will be investigated in future experiments. 

The sulfonylated and acylated PPO presents solubility characteristics which are completely different from those of the parent PPO. Table V presents the solubility of some modified structures compared to those of unmodified PPO. It is very important to note that, after sulfonylation, most of the polymers become soluble in dipolar aprotic solvents like dimethyl sulfoxide (DMSO), N,N— dimethylformamide (DMF) and N,N-dimethylacetamide (DMAC). At the same time it is interesting to mention that, while PPO crystallizes from methylene chloride solution, all the sulfonylated polymers do not crystallize and form indefinitely stable solutions in methylene chloride. Only some of the acetylated polymers become soluble in DMF and DMAC, and none are soluble in DMSO. The polymers acetylated with aliphatic acid chlorides such as propionyl chloride are also soluble in acetone. 

Due to the low solubility of the monomer 1III) in benzene, the polymerization had to be carried out at less than 10% (w/v) monomer concentration. A yield of 92% was obtained by AIBN initiation at 60°C. Ammonium persulfate and benzoyl peroxide initiators were found to be ineffective. The solubility characteristics of poly(N-pheny1-3,4-dimethylenepyrroline) are listed in Table I. The polymer was insoluble in most common solvents except for formic acid and trifluoroacetic acid. The polymer was characterized by C,H elemental analysis, IR and NMR. 

Instruments that measure scattered light, such as the Photo-Nephelometer (Coleman Instruments, Oak Brook, IL), are used to evaluate and set clarity standards for parenteral preparations. It is not possible to establish an overall standard value for all products (e.g., 30 ne-phelos) because the value itself is relative and influenced by many factors, including concentration, aging, stopper extracts, and the solubility characteristics of the raw materials. Nephelometer readings are insensitive to contamination by large (visible) particulates. 

The physical characteristics should be considered (in combination as appropriate) in relation to the proposed dosage form and route of administration. Factors to be considered extend to solubility characteristics, crystal form and properties, moisture or solvent content, particle size and size distribution (which may affect bioavailability, content uniformity, suspension properties, stability, and preclinical or clinical acceptability), polymorphism, etc. 

The physicochemical characteristics of the active ingredient in relation to the dosage form and the suitability for its intended purpose was discussed in several EPARs, particularly relating to the solubility characteristics and absorption from the gut. The compression characteristics were also mentioned in some EPARs. The possible effects of different polymorphs or evidence that only a single polymorph is used are addressed as appropriate. Different amorphous or crystalline forms are also discussed. Where affecting the dosage form, selection properties such as unpleasant taste or smell are mentioned. 

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