Miscibility and Solubility

The terms miscible and soluble are commonly used in a manner that may cause a great deal of confusion for the chromatographer. Unambiguous operational definitions for miscible and soluble are as follow  

Miscible Two components that can be mixed together in all proportions without forming two separate phases are miscible. Conversely, two components that form separate l ers when mixed are immiscible. 

Soluble A component that is present at any level in a solvent is soluble in that solvent. The maximum amount of solute A that will dissolve in a given amount of solvent B is the solubility (or solubility limit) of A in B. 

Misnomers such as partially miscible (i.e., has a low solubility) or totally soluble (i.e., miscible) only lead to confusion and their use should be avoided. 

Miscibility charts (Fig. 1.12) are handy references [23,24] but one should not read more into the chart than intended. When a solvent pair is designated immiscible, it means only that the two components will form two separate phases when they are mixed at some proportion. This does not imply that the 

---

Marsac PJ, Konno H, Taylor LS (2006a) A comparison of the physical stability of amorphous felodipine and nifedipine systems. Pharm Res 23(10) 2306-2316 Marsac PJ, ShambRn SL, Taylor LS (2006b) Theoretical and practical approaches for prediction of drug-polymer miscibility and solubility. Pharm Res 23(10) 2417-2426 Marsac PJ, Li T, Taylor LS (2009) Estimation of drug-polymer miscibility and solubility in amorphous solid dispersions using experimentally determined interaction parameters. Pharm Res 26(1) 139-151... 

P.J. Marsac, S.L. Shamblin, and L.S. Taylor, Theoretical and practical approaches for prediction of drug-polymer miscibility and solubility, Pharm Res, 23 (10), 2417-26,2006. 

In addition to hydrogen bonding, secondary-bond forces lead to the aggregation of separate particles into solid and liquid phases they are not of great importance for stable chemical compounds. However, many physical properties such as surface tension and frictional properties, miscibility and solubility are determined to a large extent by intermolecular forces. Three types of forces acting between molecules are recognized, dipole, induction, and dispersion forces. Occasionally, the term van der Waals forces is applied to the dispersion forces alone. 

---