Water-insoluble weak bases, determination

Many water-insoluble drugs are either weak bases or weak acids. There exists an equilibrium of ionized and unionized species for a weak base or a weak acid in an aqueous solution. The pH car affect the equilibrium between ionized and nonionized solute species, and consequently can have an effect on the capacity of micellar solubility. An example of this is the decreased uptake of 4-chlorobenzoic acid by polysorbate 80 micelles observed when the pH is changed from 3 to 4.4 (Collette and Koo, 1975). Another example regarding the effect of SDS micelles orKthefp atenolol, nadolol, midazolam, and nitrazepam is provided by Castro et al. (1998). Apparent acidity constants (p of the drugs were determined potentiometrically or spectrophotometrically in... 

A second difficulty enters when one of the two forms is insoluble. This must be guarded against, especially in the colorimetric determination of hydrogen ion concentration. The azo dye dimethylamino-azo-benzene (dimethyl yellow) will serve to illustrate this difficulty. Dimethyl yellow is a weak base wdth a pBOH = 10. It is very insoluble and shows a yellow color. The red colored salt, on the other hand, is much more soluble in water. In the equation... 

Salt formation is often used to enhance the solubility of insoluble compounds. The very low intrinsic solubilities of these insoluble compounds coupled with weak basicity or acidity may make the solubility determination of these salts veryLdiblt. For example, the water solubility of the phosphate salt of a very insoluble compound GW1818X was determined to be 6.8 mg/mL and the pH of the saturated solution was 5.0 (Tong and Whitesell, 1998). The solubility at this pH was shown to be limited by the solubility of the base and did not adequately represent the solubility of the salt. One way to avoid this problem is to determine solubility in a diluted acidic solution using the same acid that formed the salt with the base. The solubility can then be estimated by correcting for the common ion effect from the acid. Keep in mind that it is only from a solubility experiment at a pH less than p x that the solubility of the salt can be estimated. 

Alternatively, the total carbonyl content of a lignin preparation may be determined by reduction with either sodium or potassium borohydride. This method is based on the Lindberg-Misiorny method for the determination of carbonyl groups in carbohydrates (Lindberg and Misiorny 1952, Lindberg and Theander 1954). Both sodium and potassium borohydrides are insoluble in ether but soluble in water without decomposition. At room temperature, they effectively reduce aldehydes and ketones in aqueous and methanol solutions, in particular in weakly alkaline solutions, without simultaneously reducing olefinic double bones ... 

If feasible, add-base titrations are best carried out in aqueous media. When, however, the add or base to be determined is too weak to be titrated in water or is insoluble, then nonaqueous titrations may be attractive. An enormous literature has developed... 

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