Introduction
Solubility is the property of a solid, liquid, or gaseous
chemical substance called solute to dissolve in a solid,
liquid, or gaseous solvent to form a homogeneous
solution of the solute in the solvent. The solubility of a
substance fundamentally depends on the solvent used
as well as on temperature and pressure. The extent of
solubility of a substance in a specific solvent is
measured as the saturation concentration where
adding more solute does not increase its concentration
in the solution (1).
The solvent is generally a liquid, which can be a pure
substance or a mixture of two liquids. One may also
speak of
sona solution, Dut rarely or soluton In a gas.
The extent of solubility ranges widely, from infinitely
soluble (fully miscible) such as ethanol in water, to
poorly sol-uble, such as silver chloride in water. The
term insoluble is often applied to poorly or very poorly
soluble compounds [2].
Solubility occurs under dynamic equilibrium, which
means that solubility results from the simultaneous and
opposing processes of dissolution and phase joining
(e.g., precipitation of solids). Solubility equilibrium
occurs when the two processes proceed at a constant
rate. Under certain conditions equilibrium solubility
may be exceeded to give a so-called supersaturated
solution, which is metastable [3].
Solubility is not to be confused with the ability to
dissolve or liquefy a substance, since these processes
may occur not only because of dissolution but also
because of a chemical reaction. For example, zinc is
insoluble in hydrochloric acid, but does dissolve in it by
chemically reacting into zinc chloride and hydrogen,
where zinc chloride is soluble in hydrochloricacid.
Solubility does not also depend on particle size or other
kinetic factors; given enough time, even large particles
will eventually dissolve [4).
IUPAC defines solubility as the analytical composition
of a saturated solution expressed as a proportion ofa
designated solute in a designated solvent. Solubility
may be stated in units of concentration, molality, mole
fraction, mole ratio, and other units [5].
Extensive use of solubility from different perspective
has led to solubility being expressed in various
manners. It is commonly expressed as a concentration,
either by mass (g of solute per kg of solvent, g per dL
(100mL) of sol-vent), molarity, molality, mole fraction,
or other similar descriptions of concentration. The
maximum equilibrium amount of solute that can
dissolve per amount of solvent is the solubility of that
solute in that solvent under the specified conditions [6).
The advantage of expressing solubility in this manner is
its simplicity, while the disadvantage is that it can
strongly depend on the presence of other species in the
solvent (e.g., the common ion effect).
Saturated solutions of ionic compounds of relatively
low solubility are sometimes described by solubility
constants.
It is a case of equilibrium process. It describes the
balance between dissolved ions from the salt and
undissolved salt.
Similar to other equilibrium constants, temperature
would affect the numerical value of solubility constant.
The value of this constant is generally independent of
the presence of other species in the solvent.
The Flory-Huggins solution theory is a theoretical
model describing the solubility of polymers. The
Hansen Solubility Parameters and the Hildebrand
solubility parameters are empirical methods for the
prediction of solubility. It is also possible to predict
solubility from other physical constants such as the
enthalpy of fusion.
The partition coefficient (LogP) is a measure of
differential solubility of a compound in a hydrophobic
solvent (octanol) and a hydrophilic solvent (water).
The logarithm of these two values enables compounds
to be ranked in terms of hydrophilicity (or
hydrophobicity).
USP and BP classify the solubility regardless of the
solvent used, just only in terms of quantification and
have defined the criteria as given in Table 1 [7, 8].
The Biopharmaceutics Classification System (BCS) is a
guide for predicting the intestinal drug absorption
provided by the U.S. Food and Drug Administration.
This system restricts the prediction using the
parameters solubility and intestinal permeability.
Solubility is based on the highest-dose strength of an
immediate release product. A drug is considered highly
soluble when the highest dose strength is soluble in 250
mL or less of aqueous media over the pH range of 1 to
7.5. The volume estimate of 250 mL is derived from
typical bioequiva-lence study protocols that prescribe
administration of a drug product to fasting human
volunteers with a glass of water (9].
The intestinal permeability classification is based on a
comparison to the intravenous injection. All those
tactors are highly important, since 85% of the most sold
drugs in the USA and Europe are orally administered.
All drugs have been divided into four classes: class I—
high soluble and high permeable, class II-low soluble
and high permeable, class III-low soluble and high
permeable and class IV-low soluble and low permeable.
References
L. Lachman, H. Lieberman, and J. L. Kanig, The Theory And Practise of Industrial
Pharmacy, Lea & Febiger, 3rd edition,
1986.
M. Clugston and R. Fleming, Advanced Chemistry, Oxford Publishing, Oxford,
UK, 1st edition, 2000.
P. B. Myrdal and S. H. Yalkowsky, "Solubilization of drugs in aqueous media," in
Encyclopedia of Pharmaceutical Technology,
J. Swarbrick, Ed., p. 3311, Informa Health Care, New York, NY, USA,, 3rd
edition, 2007.
A. Martin, Solubility and Distribution Phenomena, Physical Pharmacy and
Pharmaceutical Sciences, Lippincott Williams and Wilkins, 6th edition, 2011.
"IUPAC gold book," http://goldbook.jupac.org/S05740.html.
M. Aulton, "Dissolution and solubility," in Pharmaceutics:
The Science of Dosage form Design, M. E. Aulton, Ed., p. 15, Churchill
Livingstone, 2nd edition, 2002.
The United States Pharmacopeia, USP 30-NF 25, 2007.
British Pharmacopoeia, 2009.
G. L. Amidon, H. Lennernäs, V. P. Shah, and J. R. Crison, "A theoretical basis for
a biopharmaceutic drug classification: the correlation of in vitro drug product
dissolution and in vivo bioavailability" Pharmaceutical Research, vol. 12, no. 3,
pp.213-420,1995
