Henderson-Hasselbalch equation predicting solubility

Aspirin is an acid, so it will be more ionized at alkaline pH and less ionized at acidic pH. The Henderson-Hasselbalch equation predicts that the ratio will change from 50/50 at the pH equal to the pK to 10/1 (protonated/unprotonated) at 1 pH unit more acidic than the pK. For acids, the protonated form is the nonionized, more lipid-soluble form. The answer is (D). 

When a compound forms a dimer or a higher-order oligomer in aqueous solution, the characteristic solubility-pH profile takes on a shape not predicted by the Henderson-Hasselbalch equation and often indicates an apparent pJCj that is different from the true piQ. Figure 3.3 shows several examples of sparingly-soluble... 

The Henderson-Hasselbalch equation enables predicting of how small changes in the pH values of the intestinal chyme could affect the solubility of poorly water-soluble drugs and hence their partitioning into the enterocyte membrane and their intestinal absorption. 

The in silico models derived for solubility are based on intrinsic solubility as their experimental input data. The intrinsic solubility is the solubility value determined for the neutral (i.e., uncharged) species of the compound and is generally determined at 2 pH units above the pFCa value for bases and 2 pH units below the pKa value for acids. Ampholytes are determined at their isoelectric point. The solubility values used for the model development therefore seldom reflect the apparent solubility seen in the intestinal fluids. Hence, the predicted values obtained from the models need to be transferred to an in vivo situation, for instance, by use of the Henderson-Hasselbalch equation, which takes into account the pH dependency of solubility [16],... 

The cell membrane is lipophilic in nature, and therefore acts as a barrier to drugs that are water-soluble. Those drugs that are dissociated (charged) at physiologic pH for a particular compartment will not cross the lipophilic cell membrane, and will therefore not be absorbed, or will be absorbed in lesser quantities, which are predicted by the Henderson-Hasselbalch equation. 

Experimental measurements of solubility are influenced by many different factors, including the purity of the solute and solvent, presence of cosolvents, presence of salts, temperature, physical form of the undissolved solute, ionization state, and solution pH [18]. Consequently many different definitions of solubility are in common use in the published literature. Here we discuss the intrinsic aqueous solubility, Sg, which is defined as the concentration of the neutral form of the molecule in saturated aqueous solution at thermodynamic equilibrium at a given tanperature [18-20]. Intrinsic aqueous solubility is used to calculate dissolution rate and pH-dependent solubility in models such as the Noyes-Whimey equation [21] and the Henderson-Hasselbalch equation [22, 23], respectively. Prediction of the intrinsic aqueous solubility of bioactive molecules is of great importance in the biochemical sciences because it is a key determinant in the bioavailability of novel pharmaceuticals [1, 3, 24-26] and the environmental fate of potential pollutants [27, 28],... 

---