Organic compounds, aqueous solubility enhancement

Non-aqueous microemulsions have been prepared by replacing water with formamide, a highly structured polar solvent [71]. Formamide enhances the solubility of organic compounds and is also used as a reactant. 

Class II consists of neutral organic molecules that adsorb on the electrode surface primarily because of hydrophobicity in aqueous solutions. Generally, the less soluble a molecule is, the more strongly it adsorbs. Bonding between the electrode surface and n electrons and nitrogen lone-pair electrons of the molecule can also enhance adsorption. Class II molecules can be found in virtually every category of organic compound. Typical examples are camphor, /7-butanol, and quinoline. 

Quaternary ammonium salts of dantrolene and clodanolene have been prepared, and the effect of the organic cation on the aqueous solubility has been reported (Ellis et al., 1980). It was reasoned that since the hydantoin moiety in each drug is weakly acidic, a strong base should be found for salt formation. The 13 different quaternary ammonium compounds were therefore used in the hydroxide salt form. The acid-base reaction proceeded rapidly, and the salt products were stable during recrystallization steps. Of the four salts for clodanolene, the aqueous solubilities ranged from 2- to 100-fold that of clodanolene sodium, on a mass basis. Of the 11 salts for dantrolene, the benzyl-trimethyl ammonium salt exhibited comparable solubility to that of dantrolene sodium. Among the other 10 salts were several examples that yielded enhanced solubilities of up to 1000-fold that of the sodium salt. Twelve of the Lfteen salts successfully demonstrated muscle relaxant activity when administered orally. 

It is well known that surfactants dissolved in aqueous solutions serve to enhance the solubility of ordinarily insoluble organic compounds, both solids and liquids. This phenomenon, commonly referred to as solubilization (ref. 501), has important commercial applications and as a consequence, has been the subject of considerable research (for reviews see ref. 450,502-504). Yet, as King and co-workers point out (ref. 501,505,506), less well known is the long-recognized fact that micellar solutions of surfactants are also capable of solubilizing gases (and vapors of low-molecular-weight compounds) in much the same manner as... 

Because aqueous micelles have a hydrophobic core they can, in effect, act as a second, nonaqueous phase in a system and greatly enhance the apparent water solubility of relatively insoluble hydrophobic organic compounds (HOC). Because this solubility enhancement is only observed at, or after, the onset of micelle formation, it is a criterion for identifying the formation of a micelle (3). The coincidence of the onset of a constant surface tension and the abrupt solubilization of a HCX is a definitive test for micelle formation. 

Counter-ions, usually small polar or ionic compounds, are routinely used to enhance the aqueous solubility and/or stability of the API. Because of their polarity, counter-ions are rarely resolved from the chromatographic solvent front in reversed-phase HPLC and have characteristically poor chromophores which makes detection difficult. The counter-ion can be omitted from the achiral method development sample set with minimal risk when this holds true. Analysis of counter-ions is normally performed using ion chromatography.9,10 This assay is separate from the reversed-phase assay performed to measure organic impurity levels. 

Use ofwater/DMSO mixed solvent can enhance solubility of salts in the stock solution and avoid missing valuable compounds with good aqueous solubility. Typically 1 1 water/DMSO is used to dissolve salts. Besides DMSO, water mixable solvents can sometimes be used to dissolve certain classes of compounds, such as methanol, ethanol, acetonitrile, THF, pyridine and DMF (Buchli et al., 2005). Tolerance for different organic solvents needs to be carefully evaluated for each assay during assay method development. 

The aggregates of many surface-active compounds are capable of enhancing the solubility of nonpolar organic compounds by bringing them into association with the hydrophobic portion of the amphiphilic cluster (Kile and Chiou, 1989). Humic aggregates and mieelles, in particular, may incorporate nonpolar materials such as hydrocarbons, a property that gives them the ability to act as soaps and detergents and transport hydrophobic substances into the aqueous phase (Carter and Suffer,... 

Due to a low solubility of the hydrophobic reactant in the aqueous-phase and/or of the aqueous-phase reagent in the organic phase, the rates of many heterogeneous reactions are generally low. Since the hydrotrope will enhance the solubility of the organic compound in the aqueous phase, the employment of such compounds is very useful for increasing the rates for heterogeneous reactions (11, 13). 

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