Martinez, M. N., Fahmy, R. The scientific basis for establishing solubility criteria for veterinary species. J. vet. Pharmacol. Therap. 35 (Suppl. 1), 81–86.
The relationship between factors influencing the in vitro and in vivo drug solubilization is highly dependent upon the physiology of the individual animal species and the physico-chemical properties of the drug. The solubilization of a drug in an aqueous medium is controlled by the strength of the interaction between a molecule of the active pharmaceutical ingredient (API) and the molecules of the solvent. In this regard, the stronger this interaction, the greater the likelihood that the drug will go into solution. Counteracting this solubilization process is the strength of the affinity of the solute for itself, or how tightly bound the compound is to its own solid state form. The stronger affinity of a solute for itself, the more difficult it will be for that molecule to go into solubility. However, solubility is not a universal value. Rather, it should be considered from the perspective of the interactions between the API in its solid form and the solution conditions such as: pH, the nature of the primary solvent, the presence of co-solvents, the presence of solubilizing additives, the ionic strength of the medium, incubation time, and temperature. Each of these factors needs to be considered when evaluating potential interspecies differences in drug solubility.