Solubility and Solubilization

Solubility is expressed as the concentration of a substance in a saturated solution at a defined temperature. The US Pharmacopeia (USP) gives the solubility definitions shown in Table 12-2. 

Descriptive Term Parts of Solvent Required for One Part of Solute 

However, the equilibrium solubility values are very difficult to obtain, because they are affected by many factors such as crystalline form of a substance, particle size distribution, temperature, composition of aqueous phase. 

Aqueous solubility of ionizable molecules at different pH values is an important characteristic because it indicates the potential substance behavior in the stomach and intestinal tract and its potential impact on bioavailability. Moreover, it also provides important information for formulation scientists to define the class of a drug substance in the Biopharmaceutics Classification System (BCS), a regulatory guidance for bioequivalence studies. The BCS is a scientific framework proposed by the FDA to classify drug substances based on their aqueous solubility and intestinal permeability and defines important parameters in the selection of drug candidates into development. According to the BCS, drug substances are classified as shown in Table 12-4. 

An objective of preformulation scientist is to determine the equilibrium solubility of a drug substance under physiological pH to identify the BCS class of drug candidate for further development. For BCS classification the test conditions are strictly defined by the FDA. The pH solubility profile of the test drug substance should be determined at 37°C in aqueous media with a pH in the range of 1-7.5. Standard buffer solutions described in the USP are considered to be appropriate for use in these studies. A number of pH conditions are used bracketing the pKa value for the respective test substance. For example, for a drug with a Ka of 5, solubility should be determined at 

---

Finally, the localizations of low-molecular-weight compounds requires special specimen preparation techniques, as these compounds are often diffusible, water- or organic-solvent soluble, and solubilized by conventional fixation and dehydration procedures. The reader is referred to ref. (12) for the processing of cells and tissues for the cytochemical and histochemical localization of these compounds. 

Zhong et al. (2003) studied the apparent solubility of trichloroethylene in aqueous solutions, where the experimental variables were surfactant type and cosolvent concentration. The surfactants used in the experiment were sodium dihexyl sulfo-succinte (MA-80), sodium dodecyl sulfate (SDS), polyoxyethylene 20 (POE 20), sorbitan monooleate (Tween 80), and a mixture of Surfonic- PE2597 and Witconol-NPIOO. Isopropanol was used as the alcohol cosolvent. Eigure 8.20 shows the results of a batch experiment studying the effects of type and concentration of surfactant on solubilization of trichloroethylene in aqueous solutions. A correlation between surfactant chain length and solubilization rate may explain this behavior. However, the solubilization rate constants decrease with surfactant concentration. Addition of the cosolvent isopropanol to MA-80 increased the solubility of isopropanol at each surfactant concentration but did not demonstrate any particular trend in solubilization rate of isopropanol for the other surfactants tested. In the case of anionic surfactants (MA-80 and SDS), the solubility and solubilization rate increase with increasing electrolyte concentration for all surfactant concentrations. 

Yalkaowsky SH. Solubility and Solubilization in Aqueous Media. Washington D.C. American Chemical Society, 1999. 

Yalkowsky SH. 1999. Solubility and solubilization in aqueous media. Washington, DC American Chemical Society/New York Oxford University Press. 

S. H. Yalkowsky, Solubility and Solubilization inAqeous Media, Oxford University Press, New York, 1999. 

Gadalla MAP, Saleh AM, Motawi MM. Effect of electrolytes on the solubility and solubilization of chlorocresol. Pharmazie 1974 29 105-107. 

Table 11. Solubility and Solubilization of Organic Molecules (Monomers and n-Heptyl Mercaptan) in Water and Surfactant Solutions, Respectively ...

Tenacity is determined by the force of adhesion between the particles and the substrate leaf surface. This is determined by the London-van der Waals attraction as well as the area of contact between agrochemical particles and leaf surface. The London-van der Waals attraction between the particle and the leaf surface is determined by the dispersion constant (which is related to the polarizability). Increasing the area of contact between the particles and the leaf surface enhances tenacity and for this reason smaller particles are preferred. Solubility and solubilization cem also play a major role and this requires careful measurements. 

---