the physicochemical properties of t

the physicochemical properties of the chemical leads

and has focused mainly on optimization of the in vitro

activity [1–3]. The rate at which a drug goes into the

solution when it is dissolved in an acidic or a basic

medium is proportional to the solubility of the drug.

Many drugs have different solubilities at different pHs.

These pH-dependent solubility differences lead to pH-

-dependent dissolution profiles. The solubility-pH pro-
file of drugs or amines has already been reported by

many authors [4–13].

The Henderson-Hasselbalch (HH) equation [14]

has been used many times for the mathematical des-
cription of the solubility-pH profile of drugs or amines

existing in the solution as a monomer [4,6,7].

Aqueous solubility has an essential role in the

bioavailability of oral drug formulations. There is an

established classification, namely, the biopharma-
ceutical classification system (BCS), which divides

drugs into four classes in terms of their solubility and

permeability [15]. The BCS classification correlates

the in vitro solubility and permeability to the in vivo

bioavailability.

In recent years, the problem of drug solubility in

water has become more acute and more common as

pharmaceutical companies have improved drugs for

certain therapeutic areas [16]. The accuracy of many