Drug solubility solution

It is not only the solid state of a drug that suffers from ambiguities, but also the aqueous state. The state relevant for the intrinsic solubility is the state of the saturated solution of the neutral species. Since most aqueous drug solubilities are small, direct interactions of the drug molecules are usually rare. Hence, this state is usually very similar to the state of the drug at infinite dilution in water. Most computational methods disregard saturation effects. Usually this is a good approximation, but one should keep in mind that this approximation may result in some moderate, but systematic errors at the upper end of the solubility scale. 

Fig. 3 Ternary diagram of solubility of a compound in a ternary mixture with linear solubility response. (Inset) Concentration of drug in compositions with constant concentration of B. The composition of the solute is the constant concentration of B, the concentration of A in the abscissa, and the complement concentration of the third component. The drug solubility response is linear in the A concentration in this case.

Many drugs require a certain pH range to maintain product stability. As discussed previously, drug solubility may also be strongly dependent on the pH of the solution. An important aid to the formulator is the information contained in a graph of the solubility profile of the drug as a function of pH (Fig. 2). The... 

Fig. 15.1. Factors limiting oral drug absorption. Dissolution and the aqueous drug solubility in the gastrointestinal fluids are two of the properties influencing oral drug absorption. When the drug is in solution, it can be subjected to chemical degradation and complex binding with components of the gastrointestinal fluids and/or be metabolised by...

The computation of formation constants is considered to be the most important aspect of equilibrium theory, since this knowledge permits a full specification of the complexation phenomena. Once this information is in hand, the formulator can literally define the system at a given temperature through the manipulation of solution-phase parameters to obtain the required drug solubility. 

The rate of dissolution is effected by solubility as is the actual concentration of drug in the bulk of the solution (aqueous contents of gastrointestinal tract). The concentration of drug in solution is the driving force of the membrane transfer of drug... 

When solid dosage forms such as tablets adsorb moisture, drug present on the surface will be dissolved (if it is soluble). The drug in solution on the surface of the tablet will be subject to hydrolytic decomposition, and the process will be influenced... 

Test results (mean, standard deviation, and coefficient of variation) siiin-marized in a table under solution pH, drug solubility (e.g., mg/ml), and volume of media required to dissolve the highest dose strength... 

If free base (B) is added to a certain concentration of acid, the base will form the corresponding salt with the acid. If the acid concentration is chosen so that there is an excess amount of acid in the solution (ensuring that the pH of the solution is lowerthaijViB, the solubility ofthe compound will be limited by the solubility ofthe salt ([BH]), as expressed in Equation 4.4. Knowing the amount of drug in solution, the volume ofthe solution, the solution pH, and starting acid concentration, the Ksp and the solubility ofthe salt formed situ can be calculated. 

---