Ethanol cosolvent systems

Fig. 8 Relationship between solubilization slope, a and calculated logkTo/w (via ClogP) for a variety of different solutes in ethanol cosolvent systems. (From Ref. ° l)...

Use of benzene suspensions containing a neutral rhodium(I)-DIOP complex supported on a cross-linked polystyrene (50) (cf. 13 in Section III,A) for hydrogenation of a-ethylstyrene (to 1.5% ee) and methyl atro-pate (2.5% ee) was less effective than the homogeneous system, as the ethanol cosolvent required for substrate solubility caused a collapse of the resin (296). 

Eqs. (11)-(13) illustrate the concept that acceleration or deceleration of a reaction rate upon a change in solvent polarity depends on the charge of the reactants. For example, if 8i is water and E2 is an ethanol-water mixture, two oppositely charged ions will demonstrate a reduced stability in the ethanol-water system, whereas two similarly charged reactants will demonstrate an enhanced stability. This can be understood by realizing that water provides greater insulation to ions and polar species as compared to a cosolvent-water mixture. Thus, addition of cosolvents... 

Fig. 10 Ternary cosolvent systems and resulting solubilization of spironolactone. So represents the solubility of spironolactone in a 10% ethanol/water system. Given in the figure are different concentrations of PEG-400 with varied propylene glycol or glycerin volume fractions. (From Refill ].)...

Figure 2 illustrates the kinds of particles made in this study. Here, polystyrene nanoparticles (170-nm diameter) were prepared in an ethanol cosolvent and spray-dried to produce large thin-walled particles with a wall thickness of approximately 400 nm, or 3 layers of nanoparticles. The study showed that such particles aerosolize effectively from a small inhaler and redisperse into nanoparticles once in solution. Nanoparticle aggregates were made with a variety of different materials and through many different spraydrying conditions, suggesting that these large porous nanoparticle systems are robust and functional as aerosols. 

Megrab NA, Williams AC, and Barry BW. Oestradiol Permeation Across Human Skin, Silastic and Snake Skin Membranes the Effects of Ethanol/Water cosolvent Systems. IntJPharm 1995 116 101—112. 

The dependence of the intrinsic viscosity of PVIm on the composition of ethanol/water mixtures in the presence of lithium chloride (Figure 6) is typical of cosolvent systems. In analogy with similar systems 0> 2 y/Q suppose that selective sorption does not take place at the composition corresponding to the maximum in Figure 6 (35 vol % ethanol/water) while at other compositions, the component present at lower concentration is selectively sorbed. 

A cosolvent, typically ethanol, may be used to bring drug into solution. A small number of surfactants (sorbitan trioleate, oleic acid, and lecithin) may be dispersed in propellant systems and can aid in suspension stability and in valve lubrication. 

A relatively weak rate enhancement was observed in the biphasic hydroformylation of 1-octene using Rh/tppts catalysts in the presence of cosolvents such as ethanol to enhance the solubility of the olefin in the aqueous phase and with addition of buffers (Na2C03/NaHC03) to eliminate side reactions such as the formation of acetals.31,365,366 Similarly, addition of ethanol improved the yields in the hydroformylation of 1-octene catalysed by Rh2(p-S-tBu)2(CO)2(tppts)2 species in an aqueous/organic two phase system.367 However, the high selectivity to linear aldehyde observed for neat olefin in the biphasic system (97%) decreased (to 83%) in the presence of the cosolvent.367... 

Solution-based systems are common to both nebulizers and nasal formulations. In general, water will form the greatest fraction of the formulation, but, in some cases, cosolvents such as ethanol and propylene glycol may be added for increased stability. Acidifying and alkalizing excipients may also be added to optimize pH from the perspective of the drug stability as well as the physiological effect on the airways. Similarly, iso-osmotic and iso-tonic solutions are preferred. 

Similarly to the solubility of active drugs, the solubility of surfactants that were used in CFC systems has significantly changed. Surfactant solubility in HFA 134a ranges from 0.005% to 0.02% w/v, much lower than the concentration required to stabilize suspensions (0.1-2.0% w/v) (24,42). The surfactants can be solubilized with the addition of cosolvents such as ethanol. However, it is most likely that cosolvents will be incompatible with suspension formulations because drug solubility will also be promoted and crystal growth will occur. 

Recently, a study on the effect of cosolvents on a degradation of zileuton has been reported [104], Under aqueous conditions, zileuton follows Lrst order kinetics. In this study, authors have used a ternary solvent system consisting of water, ethanol, and propylene glycol to examine both the solubility and stability of zileuton. 

In contrast to the conventional emulsions or macroemulsions described earlier are the disperse systems currently termeraiicroemulsions. The term was Lrst introduced by Schulman in 1959 to describe a visually transparent or translucent thermodynamically stable system, with much smaller droplet diameter (6-80 nm) than conventional emulsions. In addition to the aqueous phase, oily phase, and surfactant, they have a high proportion of a cosurfactant, such as an alkanol of 4-8 carbons or a nonionic surfactant. Whereas microemulsions have found applications in oral use (as described in the next chapter), parenteral use of microemulsions has been less common owing to toxicity concerns (e.g., hemolysis) arising from the high surfactant and cosolvent levels. In one example, microemulsions composed of PEG/ethanol/water/medium-chain triglycerides/Solutol HS15/soy phosphatidylcholine have been safely infused into rats at up to 0.5 mL/kg. On dilution into water, the microemulsion forms a o/w emulsion of 60-190 nm droplet size (Man Corswant et al., 1998). 

Various organic solvents were tested for the PLE-catalyzed asymmetric hydrolysis of diester (12) in a biphasic system. The results (Table 5) indicate that the reaction yields and e.e. of monoester (13) were dependent on the solvent used in the asymmetric hydrolysis. Tetrahydrofuran (THF), methyl isobutyl ketone (MIBK), hexane, and dichloromethane inhibited PLE. Lower reaction yields (28-56 M%) and lower e.e. (59-72%) were obtained using f-butyl methyl ether, dimethylformamide (DMF), and dimethylsulfoxide (DMSO) as cosolvent. Higher e.e. (>91%) was obtained using methanol, ethanol, and toluene as cosolvent. Ethanol gave highest reaction yield (96.7%) and e.e. (96%) for monoester (13). 

The effect of temperature and pH were evaluated for the PLE-catalyzed hydrolysis of diester (12) in a biphasic system using ethanol as cosolvent. It was observed that the e.e. of desired monoester (13) was increased with decreasing temperature from 25°C to 10°C. The optimum pH for asymmetric hydrolysis of diester (12) in a biphasic system using ethanol as a cosolvent was 7.2 at 10°C. 

Studies of the same system in ethanol [22] showed that this solvent favoured the formation of the CIP (A, = 690 nm), evolving already 25 ps after photolysis. For this to occur, the amine and the ketone must be cosolvated in the ground state. Indeed, decreasing stretching frequencies of the benzophenone carbonyl by addition of amine indicates ground state complex formation prior to photoinduced electron transfer (cf. Scheme 2). However, 50 to 300 ps after the laser flash, a new... 

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