‫‪SOLUBILITY‬‬

‫‪3,Mar,2023‬‬
‫‪PHYSICAL PHARMACY‬‬

‫اسماء الطلبة‬
‫الزهراء صباح علوان‬

‫رند جاسم محمد‬

‫عالء جاسب احمد‬

‫دانية عالء جاسب‬

‫امال عبدالكاظم محسن‬

INTRODUCTION
Solubility
In quantitative terms: It is the concentration of solute in a saturated solution
at a Certain temperature.

In qualitative terms: The spontaneous interaction of two or more substances

to form a homogeneous molecular dispersion.

Solubility is the ability of a solid, liquid, or gaseous chemical substance

(referred to as the solute) to dissolve in solvent (usually a liquid) and form a
solution. The solubility of a substance fundamentally depends on the solvent
used, as well as temperature and pressure. The solubility of a substance in a
particular solvent is measured by the concentration of the saturated solution.
A solution is considered saturated when adding additional solute no longer
increases the concentration of the solution.

The degree of solubility ranges widely depending on the substances, from

infinitely soluble (fully miscible), such as ethanol in water, to poorly soluble,
such as silver chloride in water. The term “insoluble” is often applied to poorly
soluble compounds. Under certain conditions, the equilibrium solubility can
be exceeded, yielding a supersaturated solution ,Solubility does not depend on
particle size; given enough time, even large particles will eventually dissolve.

The body of the drug’s crystalline form that is most stable at equilibrium can
dissolve in a given volume of a solvent at a given temperature and under a
given pressure. When the system reaches the state with the lowest energy, the
system is in thermodynamic equilibrium. A solid’s equilibrium solubility is
dependent only on the balance between the forces acting between its solution
and its lowest energy crystal form.

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Factors Affecting Solubility;
• Temperature

By changing the temperature we can increase the soluble property of a

solute. Generally, water dissolves solutes at 20° C or 100° C. Sparingly
soluble solid or liquid substances can be dissolved completely by
increasing the temperature. But in the case of gaseous substance,
temperature inversely influences solubility i.e. as the temperature
increases gases expand and escapes from their solvent.

• Forces and Bonds

“Like dissolves in like” The type of intermolecular forces and bonds vary
among each molecule. The chances of solubility between two unlike
substances are more challengeable than the like substances. For example,
water is a polar solvent where a polar solute like ethanol is easily soluble.

• Pressure
The effect of pressure on the solubility of condensed phases – solids and
liquids – is negligible.

• Molecular size
Solubility decreases as the molecular size increases. The larger the size of
molecules in a solute, the more difficult it is for solvent molecules to wrap
around them in order to dissolve them.

• Combined ion effect

The common ionic effect is a term describing the decrease in the solubility
of an Ionic compound when a salt containing an ion already present in it is
added. A state of chemical equilibrium to the mixture

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 • Mechanical factors
In contrast to the rate of dissolution, which depends mainly on
temperature, the rate of recrystallization depends on the concentration of
solute at the surface of the crystal lattice, which is preferred when the
solution is immobile. Therefore, stirring the solution prevents this build-up
and increases solubility.

• Nature of the solute

The nature of the solute and solvent and the presence of other chemical
compounds in the solution affect solubility. For example, more sugar can
be dissolved in water than salt in water. In this case, the sugar is said to be
more soluble. The volume of the solute is also an important factor. The
greater the size of the solute particles, the greater their molecular weight
and volume. It is difficult for solvent molecules to surround larger
molecules. Larger particles are generally less soluble.

• Polarity
In most cases, solutes dissolve in solvents of similar polarity. Chemists use
a popular adage to describe this property of solutes and solvents: “like
dissolves like.” Non-polar solvents do not dissolve in polar solvents and
vice versa.

Polar solvents

A drug’s solubility depends hugely on the polarity of the solvent with

which it is dissolved, i.e., its dipole moment. Solvents with polar
properties dissolve ionic solutes and other polar materials. Accordingly,
water dissolves sugars and other polyhydroxy compounds in all
proportions with alcohol but dipole moments alone are insufficient to
explain why polar substances dissolve in water. An acidic or basic
constituent also contributes to specific interactions in solutions from
the Lewis electron donor-acceptor point of view. In contrast to the
dipole moment, hydrogen bonds are a more important aspect of the
solute than polarity.

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Generally, the dielectric constant of the solvent provides a rough measure of a
solvent’s polarity. The strong polarity of water is indicated by its high
dielectric constant of 88 (at 0 °C).Solvents with a dielectric constant of less
than 15 are generally considered to be nonpolar.

The dielectric constant measures the solvent’s tendency to partly cancel the
field strength of the electric field of a charged particle immersed in it. This
reduction is then compared to the field strength of the charged particle in a
vacuum.the dielectric constant of a solvent can be thought of as its ability to
reduce the solute’s effective internal charge. Generally, the dielectric constant
of a solvent is an acceptable predictor of the solvent’s ability to dissolve
common ionic compounds, such as salts.

As a liquid, water can dissolve alcohols, aldehydes, ketones, amines, and other
nitrogen-and oxygen-containing compounds that can form hydrogen bonds
with the liquid. Solubility is determined, as we have already mentioned, by the
relative proportion of nonpolar to polar groups in a substance’s molecules. In
aliphatic alcohols, as a nonpolar chain’s length increases, a compound’s
solubility in water decreases. More than four or five carbons in a
monohydroxy alcohol, aldehyde, ketone, or acid cannot penetrate the
hydrogen bonding structure of water. As polar groups are added to water-
soluble molecules, such as in propylene glycol, glycerine, or tartaric acid, the
solubility is greatly increased. A carbon chain divided allows the nonpolar
effect to be reduced, which leads to increased water solubility. N-Butyl
alcohol, however, dissolves in water at a rate of approximately 8 g/100 mL of
water at 20°C, whereas tertiary butyl alcohol dissolves at any ratio.

Nonpolar solvents

A nonpolar solvent like hydrocarbons differs from a polar solvent

because of its molecular structure. Low dielectric constants of nonpolar
solvents prevent them from reducing the attraction between ions in
both strong and weak electrolytes. Since the solvents belong to the
group of aprotic solvents, they cannot ionize weak electrolytes nor can
they break covalent bonds. They cannot form hydrogen bridges with
non-electrolytes. Nonpolar solvents don’t dissolve ionic or polar
solutes, or only slightly dissolve them. Through induced dipole
interactions, nonpolar compounds in essence dissolve nonpolar

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 compounds with similar pressures. Molecular repulsion forces stop the
solute molecules from escaping into the solution. All these solvents can
dissolve oils and fats, including carbon tetrachloride, benzene, and
mineral oil. Nonpolar solvents are also suitable for dissolving alkaloidal
bases and fatty acids.

Semi polar solvents

In nonpolar solvent molecules, such as benzene, semi polar

solvents can give the molecules some degree of polarity, so that
they become soluble in semi polar solvent molecules, such as
ketones and alcohols. In general, semi polar compounds serve as
intermediate solvents, eliminating polarity from nonpolar liquids
and bringing them into miscibility. In this way, acetone facilitates
ether’s solubility in water. Water–castor oil mixtures were
studied by Loran and Guth as intermediate solvents. The
combination of peppermint oil and propylene glycol has been
shown to enhance the mutual solubility of the two. The same
investigation was conducted with benzyl benzoate and water.

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Methods of solubility ;
1. Solvent combination (co-solvent)
2. Salt formation (PH control)
3. Solubilisation by complexation

• Solvent combination ( co-solvent)

A co-solvent system is a mixture of miscible
solvents, which is often used to dissolve water-
insoluble drugs.

• Salt formation ( PH control)

Salt formation is the most common and effective method of increasing
solubility and dissolution rates of acidic and basic drugs.pH control is
the process of adding an alkaline or acidic substance to a liquid in order
to bring the measured pH within a desired range.

• Solubilisation by complexation
The formation of a complex ion has an affect on solubility. In salts,
introducing a ligand that is able to form a stable complex will increase
its solubility. This is due to the metal cations that are removed from the
solubility equilibria in order to form the complex ion .

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 • The aim of solubility experiment;

A major goal of this experiment is to learn how to make

predictions about whether or not a substance will be
soluble in a given solvent.

• Tools and materials:-

• Conical flask
• Beaker
• Pipette
• Burette
• Water H2O
• Salicylic acid C6H4(OH)CO2H
• Ethanol C2H6O
• Sodium carbonate Na₂CO₃ or sodium hydroxide NaOH
• potassium iodide KI

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PROCEDURE

• Solvent Combination (co-solvent):

1. Put 0.1g of salicylic acid in conical flask.
2. Add 10ml of water, and shake well.
3. Add alcohol (ethanol) by pipette drop by drop until all
crystals are disappeared. 4)Calculate v/v% of ethanol
which need to dissolve 0.1g of salicylic acid.

• pH Control:
1. Put 0.1g of salicylic acid in conical flask.
2. Add 10ml of water, and shake well.
3. Add 0.1g sodium carbonate or sodium hydroxide and
shack well until all crystals are disappeared.

• Solubilisation by complexation
1. Put 0.1 g of iodine in a conical flask.
2. Add 10 mL water to the flask, shake the flask and observe the result.
3. Add 0.2 g of potassium iodide (KI) to the flask and observe the
result.

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RESULT

• Salicylic acid when dissolved in water, a very small

amount of it dissolves in water (partly dissolved ) ,and the
rest is precipitated to prevent the process of precipitation
of a poorly soluble salt, it is necessary to add a little
substance to help reduce the concentration of one of the
ions, for this we use ethanol, which acts as a catalyst or
Solvent Combination (co-solvent), so When ethanol is
added to a solution of salicylic water, the salicylic acid
soluble. ✔️

• Added sodium carbonate or sodium hydroxide to form a

salt that is easily soluble in water, So that most of the
weak electrolytes can be retained in solution by adjusting
the pH to preserve them the drug is in ionized form.✔️

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DATA ;

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DISCUSSION ;

• Why salicylic acid is insoluble in water?

Salicylic acid is not soluble in water because it is not polar, the way water
molecules are. For one substance to be soluble in another, remember the
rule, “like dissolves like”. In other words, a polar molecule is likely to
dissolve in a polar solvent, and a nonpolar molecule will dissolve in a
nonpolar solvent, but a polar molecule will probably not dissolve in a
nonpolar solvent. Salicylic acid has a phenyl ring on it that does not
interact with water molecules, but the carboxyl and OH groups may
interact with water molecules, creating a partial solubility. This means that
some salicylic acid dissolves in water. The solubility of salicylic acid in
water (at room temperature) is a little over 2 grams in 1 liter of water.

• Why does water dissolves phenols, alcohols, aldehydes, ketones,

amines?

Water is Polar solvent dissolve ionic solutes and other polar substances
because containing compounds that can form hydrogen bonds with
water.

• Wy we use salicylic acid?

Salicylic acid is not readily soluble in water at room temperature. It

needs to be converted to salicylate if you want it to dissolve completely
in water. Its solubility is also dependent on the pH of the solvent. It
dissolves very well in water at a pH level of 3, So it does not react with
water This is why it is used to determine the solubility of solid salts that
are poorly soluble when adding water and auxiliary factors.

• Why we use Solvent Combination (co-solvent)?

A drug is insoluble or slightly soluble in certain solvent, we can increase

the solubility by addition another solvent.

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 • why is ethanol added to salicylic acid solution?

Because salicylic acid is insoluble in water, when the concentration of

ethanol decreases, a flocculent precipitate will form in high
concentration salicylic acid-containing groups. Adding ethanol to 50%
concentration can completely dissolve 10% salicylic acid.

And ethanol may be a better solvent to separate and purify salicylic acid
from solutions.

• What is PH adjusting?
A pH adjuster is a chemical used to alter the pH or Potential Hydrogen
level. pH (Potential Hydrogen) is the measurement of the activity of the
hydrogen ion or how basic or acidic something is. By adding a pH
reagent such as an acid you can drive pH downward.

• why is sodium bicarbonate added to salicylic acid?

To form a salt that is easily soluble in water, So that most of the weak
electrolytes can be retained in solution by adjusting the pH to preserve
them the drug is in ionized form.

• What is the reaction between sodium hydroxide and salicylic acid?

Two equivalents of sodium hydroxide will neutralize both, the carboxylic

acid and hydroxyl group of salicylic acid to produce sodium 2-
hydroxybenzoate and water as the products.

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SOURCES;
1. Physical Chemistry Chemical Physics 2019,page 21
2. Chemical Engineering Journal 2018,page 331
3. ”On the Theory of Solute Solubility in Mixed Solvents”. The Journal of
Physical Chemistry , page 112 , 117
4. Journal of Chemical Physics, volume 44, issue 6, page 2322.
5. I. Lee and J. Lee (2012): “Measurement of mixing ratio and volume
change of ethanol-water” •”Pharmacopeia of the United States of
America, 32nd revision, and the National Formulary, 27th edition,” 2009,
pp.1 to 12.binary mixtures using suspended microchannel resonators.”
SENSORS, volume 2012, pages 1-3
6. Carl L. Yaws, Chemical Properties Handbook, McGraw-Hill, New York,
1999, page 567
7. Handbook of Chemistry and Physics (27th ed.). Cleveland, Ohio:
Chemical Rubber Publishing Co.
8. Saether; P. De Caritat, eds. (2016). Geochemical processes, weathering
and groundwater recharge in catchments. Rotterdam: Taylor & Francis.
P. 6.

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