Cosolvents systemic effects

S Wittaya-Areekul, S Nail. Freeze-drying of tert-butyl alcohol/water cosolvent systems effects of formulation and process variables on residual solvents. Journal of Pharmaceutical Sciences 87 491, 1998. 

For cosolvent systems, because the heat of solution in different solvent systems is generally different, the temperature effect on solubility in these systems is also different. Detailed solubility mapping in the solvents of interest, including the effect of pH (forionizable compounds), temperature,... 

Numerous methods have been proposed to predict or describe the effect of a particular cosolvent system ° on drug solubility. A practical cosolvent model was developed by Yalkowsky and coworkers " by assuming the mixed solvent system is a linear combination of the pure components. They found that this approach yields the log-linear relationship... 

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. 

Cosolvents. The effect of organic solvents on the physical properties of water is a historically useful phenomenon and well defined for countless industrii and scientific applications. This phenomenon has always been ignored in the chemical models available for generi usage. Cosolvents affect the dielectric constant of the water, impacting activity coefficient calculations, hydration of species, and adsorption computations. Application of current chemical codes to environmental contamination investigations will require a capability for simulating the effect of a wide variety of miscible solvents on the aqueous system. As the currently available codes are refined, subroutines should be added that address this issue. 

When a miscible solvent is added to water, the solvent increases the solubility and decreases the sorption of nonionic organic compounds by reducing the net polarity of the solution. The effect of a cosolvent depends on the nature of the solute and the solvent-cosolvent system, but there is usually a log-linear relationship between chemical aqueous solubility and the volumetric fraction of water-miscible solvent (Wood et al, 1990 Bouchard, 2002). 

Erbeldinger M, Ni X, HaUing PJ (1998) Effect of water and enzyme concentration on thennolysin-catalyzed solid-to-sohd peptide synthesis. Biotechnol Bioeng 59(l) 68-72 Fernandez-Lafuente R, Alvaro G, Blanco RM et al. (1991) EquUibrium controlled synthesis of cephalotin in water-cosolvent systems by stabiDzed peniciUin acylase. Appl Biochem Biotechnol 27 277-289... 

PLA/15% HMW PCL at a blend ratio of 1/1 using chloroform/methanol cosolvents were only selected to examine TCH drug release and subsequent fiber biodegradability due to produced homogeneous fibers and better PLA and PCL miscibility when compared with other cosolvent systems. Furthermore, the variation in the degree of crystallinity between PLA/15% HMW PCL and PLA/9% HMW PCL was another reason to study that effect. 

Cationic surfactants may be used [94] and the effect of salinity and valence of electrolyte on charged systems has been investigated [95-98]. The phospholipid lecithin can also produce microemulsions when combined with an alcohol cosolvent [99]. Microemulsions formed with a double-tailed surfactant such as Aerosol OT (AOT) do not require a cosurfactant for stability (see, for instance. Refs. 100, 101). Morphological hysteresis has been observed in the inversion process and the formation of stable mixtures of microemulsion indicated [102]. 

In the following text, examples of solvent effects on enzyme selectivity, referred either to systems based (i) on water-miscible organic cosolvents added to aqueous buffers or (ii) on organic media with low water activity, are discussed. 

We have reported the first example of a ring-opening metathesis polymerization in C02 [144,145]. In this work, bicyclo[2.2.1]hept-2-ene (norbornene) was polymerized in C02 and C02/methanol mixtures using a Ru(H20)6(tos)2 initiator (see Scheme 6). These reactions were carried out at 65 °C and pressure was varied from 60 to 345 bar they resulted in poly(norbornene) with similar conversions and molecular weights as those obtained in other solvent systems. JH NMR spectroscopy of the poly(norbornene) showed that the product from a polymerization in pure methanol had the same structure as the product from the polymerization in pure C02. More interestingly, it was shown that the cis/trans ratio of the polymer microstructure can be controlled by the addition of a methanol cosolvent to the polymerization medium (see Fig. 12). The poly(norbornene) prepared in pure methanol or in methanol/C02 mixtures had a very high trans-vinylene content, while the polymer prepared in pure C02 had very high ds-vinylene content. These results can be explained by the solvent effects on relative populations of the two different possible metal... 

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). 

As a matter of fact, cosolvents such as primary alcohols, polyols, di-methylformamide and dimethyl sulfoxide are now almost routinely used to perturb the overall reactions and elementary equilibria or rate processes of the highly organized systems carrying out DNA, RNA, and protein synthesis. However, in spite of the fact that such systems respond well and in a reversible way to these perturbations, cosolvent effects remain relatively poor probes of reaction mechanisms (Hamel, 1972 Voigt et al., 1974 Ballesta and Vasquez, 1973 Crepin et ai, 1975 Nakanishi et al., 1974 Brody and Leautey, 1973). The most common result reported upon addition of increasing amounts of cosolvents is a bell-shaped curve equilibria and rate processes are first stimulated and... 

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