Solubilization weak acids

Sheng, J. J., N. A. Kasim, R. Chandrasekharan, and G. L. Amidon. 2006. Solubilization and dissolution of insoluble weak acid, ketoprofen Effects of pH combined with surfactSnt. J. Pharm. Sci. 29 306-314. 

Micellar solutions of detergents such a sulfonates, phenolates and salicylates enhance the solubilizing properties of succinimide additives. For small concentrations of about 0.25% w/w sulfonate and 2.8% succinimide, a synergistic effect is observed, but for high sulfonate concentrations, the quantity of acid solubilized is less than that observed for succinimide alone (Bradley and Jaycock, 1972). A different mechanism exists for the solubilization of those weak acids and for strong acids. The different interaction between the amine groups in the polar head of a succinimide micelle and a weak acid (WH), and for a strong acid (SH), indicates that the weak acid is much better solubilized as ... 

Solubilization of Weak Acids or Weak Bases in Cosolvent Systems... 

The total solubility of weak acid in a water/cosolvent system [HA] ot can be determined by the solubility of the un-ionized species in water, the solubilizing powers, the hydrogen ion concentration, and the dissociation constant of the weak acid. Equation (3.49d) illustrates that the total solubility of the weak acid will increase exponentially with respect to the volume fraction of the cosolvent. Even though the solubilizing power of the cosolvent for the un-ionized species is usually larger than that of the ionized species, the solubilization of the ionized species is very important in determining the total solubility when pH - pKa > oIIA - oa. ... 

Thus, there appears to be something unique about the weakly acidic phenolic materials. In addition to phenol itself, 3,5-xylenol, 2-naphthol, phenol-naphthalene (1 1). and cresylic acid all show ability to solubilize the coal. Recently, Darlage and Bailey have studied the phenol catalyzed depolymerization of a Kentucky coal (Pond Creek Seam, Pike County). (16) This coal does not depolymerize efficiently and would compare with the poorest coals tested with data shown in Table II. These authors also show that phenolic solvents in general cause solvation of coal whereas non-phenolic aromatics add to coal but do not solubilize the coal. 

Once the values of pffa, [Ca], and pH are known, the total amount of drug solubilized in water at a specific pH can be calculated. Substantial increases in aqueous solubility can be achieved simply by adjusting the pH. In fact, adjustment of greater than 3 pH units in the appropriate direction (weak bases solubilize at lower pH and weak acids at higher pH) away from the p/fa may result in more than 1000-fold increases over the intrinsic solubility of a drug. Analogous equations can be written for weak bases such as Eqs. (5) and (6). 

Under the proper conditions, the solubility of an ioniz-able drug can increase exponentially by adjusting the pH of the solution. From a structural point of view, a drug that can be efficiently solubilized by pH control should be either a weak acid with a low pATg or a weak base with a high p Tg. Note that the effect of pH on solubilization is independent of the value of the solubility of the unionized form of the drug. In other words the solubility of an unionized acid with a pA a of 4.2 and a solubility of l.Omg/ml and one with the same p/fa and a solubility of 0.001 mg/ml will both be increased by a factor of 1001 at pH 7.4. 

The relationship between adsorption of surfactants on the one hand and of small organic molecules on the other has been also studied. At sufficiently high adsorption density, the adsorbed surfactant is able to solubilize water insoluble organic compounds, and this phenomenon is termed adsolubilization. This may result in uptake of certain adsorbates which do not adsorb on the material of interest in the absence of surfactant, Adsolubilization of weak acids and bases is strongly pH dependent and it often shows a maximum at pH close to the pKa of the solute. 

There are various methods that can be used to measure the biological availability of magnesium supplements these can involve in vitro or laboratory studies such as the rate of solubilization in rumen fluid or weak acid solution. This method of study is less time consuming and less costly than pursuing animal studies, although in vivo methods are preferred. 

In effect, the titration becomes one of replacing the HB cation by the Na of the titrant up to the endpoint. After the endpoint, the excess OH" causes the conductance to rise rapidly. An additional advantage of the use of a weak base is its ability to solubilize many sUghtly soluble weak acids that otherwise require non-aqueous solvents, in which generally poorer endpoints are obtained. Figure 5.7 compares titrations of a very weak acid, such as phenol, with and without the addition of NH4OH. 

Since the water pool serves as the reaction medium, the characteristics of the solubilized water present within the polar core would be expected to influence the nucleation process. The properties of the water pool of relevance here include the proportion of free versus bound water molecules and the polarity of the solubilized water. When a volume of aqueous solution containing a given reactant is introduced into an initially dry surfactant-oil solution, a portion of the added water molecules will be immobilized through hydration of the surfactant polar groups. With increasing immobilization of the water molecules, reactions that require ionic dissociation (e.g., those involving weak acids and bases) will become less favorable. Thus, under such circumstances, an increase in the water content should enhance nucleation (see Fig. 5e). In the case of reactions involving hydrolysis, water serves as a reactant, and therefore a decrease in the availability of free water will lead to lowered nucleation rates (Fig. 5e). 

Synthesis of oximes and amines. Copper salts solubilized in aqueous alkyl polyamines solvents have been found to promote the homogeneous reduction of nitroalkanes to oximes by CO at atmospheric pressure and 85 C in good yields and conversion(9. Catalysis is favoured by the use of copper salts of weak acids solubilized in alkylpolyamlnes solvents of pKa > 9.2. The suggested reaction path involves the formation of a solvated cuprous carbonyl complex, which by combination with the nitroalkane anion gives a copper-nitroalkane complex ... 

Gum arahic occurs neutral or as a weakly acidic salt. Counter ions are Ca +, Mg" and K" ". Solubilization in 0.1 mol/1 HCl and subsequent precipitation with ethanol yields the free acid. Gum arahic exhibits marked emulsifying and film-forming properties, which are caused not only by its stracture, but also by the slight admixture (ca. 2%) of a protein. The serine and threonine residues of this protein are thought to be covalently bound to the carbohydrate. 

Further investigation of phase transfer catalysis, a phenomenon where quaternary ammonium salts catalyse reactions in aqueous-organic two-phase systems, has confirmed that the function of the ammonium ion is to solubilize the reagent/substrate in the organic phase. The use of phase transfer catalysis in the alkylation of weak acids such as diethyl malonate has been described other examples - - of this phenomenon are cited above. 

An excellent solubilization of the active factor can be reached by extracting it in aqueous solution at pH 10. In such a way 80fc of the product and more than 95 of the biological activity is solubilized. Nevertheless we can notice that Urogastrone is very sensitive to alkaline pH. In alkaline conditions its activity is rapidly lost. On the other hand it is much more stable in a neutral or weakly acid solution. 

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