Solutions

A solution may be defined as a mixture of two or more components that form a single phase that is
homogeneous down to the molecular level. The component that determines the phase of the solution is termed
the solvent; it usually (but not necessarily) constitutes the largest proportion of the system. The other
component(s) are termed solute(s) and these are dispersed as molecules or ions throughout the solvent, i.e. they
are said to be dissolved in the solvent. Example; mixture of salt and water. Water is the most common solvent,
although organic solvents are used in combination with water or on their own.

The transfer of molecules or ions from a solid state into solution is known as dissolution. Fundamentally, this
process is controlled by the relative affinity between the molecules of the solid substance and those of the
solvent. The solvent and the solute must have similar intermolecular interactions. When this is the case, the
individual particles of solvent and solute can easily mix so intimately that each particle of solute is surrounded
by particles of solvent, forming a solution. However, if two substances have very different intermolecular
interactions, large amounts of energy are required to force their individual particles to mix intimately, so a
solution does not form.

This process leads to a simple rule of thumb: like dissolves like. Solvents that are very polar will dissolve
solutes that are very polar or even ionic. Solvents that are nonpolar will dissolve nonpolar solutes. Thus water,
being polar, is a good solvent for ionic compounds and polar solutes like ethanol (C 2H5OH). However, water
does not dissolve nonpolar solutes, such as many oils and greases
Solubility: The extent to which the dissolution proceeds under a given set of experimental conditions is referred
to as the solubility of the solute in the solvent. The solubility of a substance is the amount of it that passes into
solution when equilibrium is established between the solute in solution and the excess (undissolved) substance.
The solution that is obtained under these conditions is said to be saturated. A solution with a concentration less
than that at equilibrium is said to be unsaturated. Solutions with a concentration greater than equilibrium can be
obtained in certain conditions; these are known as supersaturated solutions.
Since the above definitions are general ones, they may be applied to all types of solution involving any of the
three states of matter (gas, liquid, solid) dissolved in any of the three states of matter, i.e. solid-in-liquid, liquid-
in-solid, liquid-in-liquid, solid-in-vapour, etc. However, when the two components forming a solution are either
both gases or both liquids, then it is more usual to talk in terms of miscibility rather than solubility. Other than
the name, all principles are the same.
 Types of solution
Solvent phase Solute phase Example
Gas Gas Air
Liquid Gas Carbonated beverages
Liquid Liquid Ethanol in water
Liquid Solid Salt in water
Solid Gas H2 gas absorbed by Pd metal
Solid Liquid Hg (l) in dental filling
Solid Solid Alloy metals

Expressions of concentration
1. [Link]
Concentrations are often expressed simply as the weight or volume of solute that is contained in a given weight
or volume of the solution. The majority of solutions encountered in pharmaceutical practice consist of solids
dissolved in liquids. Consequently, concentration is expressed most commonly by the weight of solute
contained in a given volume of solution. Although the SI unit is kg m -3 the terms that are used in practice are
based on more convenient or appropriate weights and volumes. For example, in the case of a solution with a
concentration of 1 kg m-3 the strength may be denoted by any one of the following concentration terms,
depending on the circumstances: 1 g L-1, 0.1 g per 100 mL, 1 mg mL-1, 5 mg in 5 mL or 1 µg µL-1.
2. Percentage
Pharmaceutical scientists have a preference for quoting concentrations in percentages. The concentration of a
solution of a solid in a liquid is given by:
Concentration in % wv = weight of solute/volume of solution ×100
Equivalent percentages based on weight (w) and volume (v) ratios (expressed as % v/w, % v/ v and % w/w) can
also be used for solutions of liquids in liquids and solutions of gases in liquids.

The mass/mass percent (% m/m) is defined as the mass of a solute divided by the mass of a solution times 100:
% m/m = mass of solute/mass of solution×100%

e.g. A saline solution with a mass of 355 g has 36.5 g of NaCl dissolved in it. What is the mass/mass percent
concentration of the solution?

We can substitute the quantities given in the equation for mass/mass percent:
% m/m = 36.5g/355g×100% = 10.3%
A hybrid concentration unit, mass/volume percent (% m/v), is commonly used for intravenous (IV) fluids. It is
defined as the mass in grams of a solute, divided by volume in milliliters of solution times 100:
% m/v = mass of solute (g)/volume of solution (mL)×100%
3. Parts

Pharmacopoeias give information on the approximate solubility of official substances in terms of the number of
‘parts’ of solute dissolved in a stated number of ‘parts’ of solution. Use of this method to describe the
concentration of a solution of a solid in a liquid suggests that a certain number of parts by weight (g) of solid are
contained in a given number of parts by volume (mL) of solution. In the case of solutions of liquids in liquids,
parts by volume of solute in parts by volume of solution are intended, whereas with solutions of gases in
liquids, parts by weight of gas in parts by weight of solution are inferred. These units are used for expressing the
concentrations of extremely dilute solutions are parts per million (ppm) and parts per billion (ppb). Both of
these units are mass based and are defined as follows:
ppm = mass of solute /mass of solution ×1,000,000
ppb = mass of solute/mass of solution×1,000,000,000
Similar to parts per million and parts per billion, related units include parts per thousand (ppth) and parts per
trillion (ppt).
In aqueous solutions, 1 ppm is essentially equal to 1 mg/L, and 1 ppb is equivalent to 1 µg/L.
4. Molarity

Molarity (M) is the concentration of a solution expressed as the number of moles of solute per liter of solution.
The unit of molarity (M) is mol/L.

Molarity = moles of solute / liters of solution

For example, if you have 1.5 mol of NaCl dissolved in 0.500 L of solution, its molarity is therefore
1.5 mol NaCl /0.500 L solution = 3.0 M NaCl

Example; what is the molarity of an aqueous solution of 25.0 g of NaOH in 750 mL?

Before we substitute these quantities into the definition of molarity, we must convert them to the proper units.
The mass of NaOH must be converted to moles of NaOH. The molar mass of NaOH is 40.00 g/mol:
25.0g NaOH ×1 mol NaOH / 40.00g NaOH = 0.625 mol NaOH

Next, we convert the volume units from milliliters to liters:

750 mL× 1L/ 1,000mL= 0.750 L
Now that the quantities are expressed in the proper units, we can substitute them into the definition of molarity:

M = 0.625mol NaOH / 0.750L = 0.833M NaOH

5. Molality

Molality (m) is defined as the number of moles of solute per kilogram of solvent. The SI unit for molality is
mol/kg

molality = moles of solute/kilograms of solvent

Q: What is the molality of a solution if 124.2 grams of NaOH are dissolved in 1.00 liter of water? (The density

of water is equal to 1.00 )

Answer: Water is referred to as the universal solvent and the density is typically given as 1.00 grams per liter.
This makes for an easy conversion from liters to kilograms.
In this problem the 124.2 grams of NaOH will need to be converted to moles (for moles of solute) and one liter
of water will need to be converted into kilograms (for kilograms of solvent) using the density.
First, find the molar mass of NaOH.

NaOH = 22.99 + 16.00 + 1.01 = 40.00

Second, convert the grams of NaOH into moles, using the molar mass.

= 3.105 moles of NaOH

Third, convert the liter of water into kilograms using the density.

= 1.00 kilograms
Finally, use the molality equation to solve.

6. Molar fraction: This is often used in theoretical considerations and is defined as the number of moles
of solute divided by the total number of moles of solute and solvent, i.e.:
n1
Mole fraction of solute (x1) =
n 1+ n 2
where n1 and n2 are the numbers of moles of solute and solvent, respectively.
Raoult’s Law

In 1986, it was a French Chemist, Francois Marte Raoult who proposed a relationship between partial pressure and
mole fraction of volatile liquids. According to the law, ‘the mole fraction of the solute component is directly
proportional to its partial pressure’. OR
Raoult’s Law states that the partial vapour pressure (p) exerted by a volatile component in a solution at a given
temperature is equal to the vapour pressure of the pure component at the same temperature ( po) multiplied by
its mole raction in the solution (x), i.e.: p= p0 x
On the basis of Raoult’s Law, liquid-liquid solutions can be of two types. They are:
 Ideal Solutions
 Non-ideal Solutions
Ideal Solutions
The solutions which obey Raoult’s Law at every range of concentration and at all temperatures are Ideal Solutions.
We can obtain ideal solutions by mixing two ideal components that are, solute and a solvent having similar
molecular size and structure.
For Example, consider two liquids A and B, and mix them. The formed solution will experience several
intermolecular forces of attractions inside it, which will be:
 A – A intermolecular forces of attraction
 B – B intermolecular forces of attraction
 A – B intermolecular forces of attraction
The solution is said to be an ideal solution, only when the intermolecular forces of attraction between A – A, B – B
and A – B are nearly equal.
Characteristics of Ideal Solutions
Ideal Solutions generally have characteristics as follows:
 They follow Raoult’s Law. This implies that the partial pressure of components A and B in a solution will
be PA = PA0 xA and PB = PB0 xB . PA0 and PB0 are respective vapour pressure in pure form. On the other hand,
xA and xB are respective mole fractions of components A and B
 The enthalpy of mixing of two components should be zero, that is, Δmix H = 0. This signifies that no heat is
released or absorbed during mixing of two pure components to form an ideal solution
 The volume of the mixing is equal to zero that is, Vmix V = 0. This means that total volume of solution is
exactly same as the sum of the volume of solute and solution. Adding further, it also signifies that there will
be no contraction or expansion of the volume while the mixing of two components is taking place.
 The solute-solute interaction and solvent-solvent interaction is almost similar to the solute-solvent
interaction.
Examples of Ideal Solutions
 n-hexane and n-heptane  Chlorobenzene and Bromobenzene
 Bromoethane and Chloroethane  Ethyl Bromide and Ethyl Iodide
 Benzene and Toluene  n-Butyl Chloride and n-Butyl Bromide
 CCl4 and SiCl4  ethanol and methanol
Non-Ideal Solutions
The solutions which don’t obey Raoult’s law at every range of concentration and at all temperatures are Non-Ideal
Solutions. Non-ideal solutions deviate from ideal solutions and are also known as real Solutions.

Characteristics of Non-ideal Solutions

Non-ideal solutions show characteristics as follows:
 The solute-solute and solvent-solvent interaction is different from that of solute-solvent interaction
 The enthalpy of mixing that is, Δmix H ≠ 0, which means that heat might have released if enthalpy of mixing
is negative (Δmix H < 0) or the heat might have observed if enthalpy of mixing is positive (Δmix H > 0)
 The volume of mixing that is, Vmix V ≠ 0, which depicts that there will be some expansion or contraction in
the dissolution of liquids
Non-ideal solutions are of two types:
 Non-ideal solutions showing positive deviation from Raoult’s Law
 Non-ideal solutions showing negative deviation from Raoult’s Law
i) Positive Deviation from Raoult’s Law
Positive Deviation from Raoult’s Law occurs when the vapour pressure of the component is greater than what is
expected in Raoult’s Law. For Example, consider two components A and B to form non-ideal solutions. Let the
vapour pressure, pure vapour pressure and mole fraction of component A be PA , PA0 and xA respectively and that of
component B be PB , PB0 and xB respectively. These liquids will show positive deviation from Raoult’s Law when:
 PA > PA0 xA and PB > P0B xB, as the total vapour pressure (PA0 xA + P0B xB) is greater than what it should be
according to Raoult’s Law.
 The solute-solvent forces of attraction is weaker than solute-solute and solvent-solvent interaction that is, A
– B < A – A or B – B
  The enthalpy of mixing is positive that is, Δmix H > 0 because the heat absorbed to form new molecular
interaction is less than the heat released on breaking of original molecular interaction
 The volume of mixing is positive that is, Vmix V > 0 as the volume expands on the dissolution of components
A and B
Examples of Positive Deviation
Following are examples of solutions showing positive deviation from Raoult’s Law:
 Acetone and Carbon disulphide  Methyl Alcohol and Water
 Acetone and Benzene  Acetone and Ethanol
 Carbon Tetrachloride and Toluene or  Ethanol and Water
Chloroform
Negative Deviation from Raoult’s Law
Negative Deviation occurs when the total vapour pressure is less than what it should be according to Raoult’s Law.
Considering the same A and B components to form a non-ideal solution, it will show negative deviation from
Raoult’s Law only when:
 PA < PA0 xA and PB < P0B xB as the total vapour pressure (PA0 xA + P0B xB) is less than what it should be with
respect to Raoult’s Law
 The solute-solvent interaction is stronger than solute-solute and solvent-solvent interaction that is, A – B >
A – A or B – B
 The enthalpy of mixing is negative that is, Δmix H < 0 because more heat is absorbed when new molecular
interactions are formed
 The volume of mixing is negative that is, Vmix V < 0 as the volume decreases on the dissolution of
components A and B
Following are examples of solutions showing negative deviation from Raoult’s Law
 Chloroform and Benzene  Nitric Acid ( HNO3) and water
 Chloroform and Diether  Acetic Acid and pyridine
 Acetone and Aniline  Hydrochloric Acid ( HCl) and water

Colligative Properties of Liquids

Colligative properties are those of a liquid that depend on the number of solute particles and not on the
concentration of the solution. These properties are studied in liquids. According to these properties, mixing a non-
volatile solution with a volatile solution decreases the relative vapor pressure of the solution.
Furthermore, this decrease in the vapor pressure can be further used to quantify and study the properties of all
liquid solutions. Specifically, colligative properties are dependent upon the solute particles present in a given
solution. Derived from the Latin word ‘Coligare’, the word, colligative refers to ‘binding together’.

There are four colligative properties: relative lowering of vapor pressure, elevation of boiling point, depression of
freezing point, and osmosis and osmotic pressures.
1) Relative Lowering of Vapour Pressure
In a closed container, a liquid will evaporate until an equal amount of molecules are returning to the liquid state
as they are escaping into the gas phase. The pressure of the vapor phase above the liquid at this point is called
the equilibrium vapor pressure. This vapor pressure is dependent on several factors, including the temperature
of the system (kinetic energy is required to help the molecules escape into the gas phase), the pressure of the
system (high pressure can keep the gas contained in the liquid e.g. a bottle of coke), and also the intermolecular
forces of the liquid itself (stronger bonds will require more kinetic energy to break slowing the evaporation
process, lowering the overall vapor pressure of the system).
When a solute is added to the solvent, some of the solute molecules will take up spaces at the surface of the
liquid, this will limit the number of solvent molecules at the surface. Since only solvent molecules located at the
surface can escape (evaporate), the presence of the solute lowers the number of solvent molecules coming and
going and therefore lowers the equilibrium vapor pressure. As per the laws devised by scientists (Raoult’s law) at
that time, reduction in Vapour Pressure = Vapour Pressure of Pure Solvent – Vapour Pressure of Solvent. It is
through this equation that we can determine the ultimate molar mass of a solute.
(Psolvent = Xsolvent - Posolvent)
The pressure obtained from this equation is the new equilibrium vapor pressure of the system with the solute
included. If you want to know how much change has taken place, you will need to look at the difference
between the new Psolvent and the original Posolvent of the pure solvent (in other words subtract one from the
other) DP = Psolvent - Posolvent = change in the vapor pressure of the system. For almost all non-volatile solvents,
this change will be a negative value.
2) Elevation of Boiling Point
The normal boiling point of a liquid is defined as the temperature at which the vapor pressure of the liquid is
equal to standard pressure (1 atm). If we change the external pressure from 1 atm lower or higher, the boiling
point changes as well. The boiling point is then simply the temperature at which the vapor pressure of the
solvent equals the pressure of the surroundings.
By adding solutes to a solvent, the solute molecules will take up positions at the surface of the liquid which will
depress the vapor pressure. So the vapor pressure of the liquid has to be raised in order to reach the boiling point
so this must mean more energy will be required to reach the same vapor pressure. Input of more energy equates
to the input of heat in this type of system, so the boiling point temperature must be higher to obtain the same
vapor pressure. Adding a non-volatile solute to a solution therefore raises the boiling point of that solution.
When a solute is dissolved in a solvent, the boiling point of the solution is raised according to the equation:
DT = iKbm
DT= change in temperature
i = the van't Hoff factor, which is the number of particles into which the solute dissociates
m = the molality, which is the moles of solute per kilograms of solvent
Kb = the molal boiling point constant (for water, Kb = 0.5121oC/m)
3) Depression of Freezing Point

The normal freezing point of a liquid is the temperature at which a liquid becomes a solid at 1 atm. A more
specific definition of freezing point is the temperature at which solid and liquid phases coexist in equilibrium.
Let's see if we can figure out why the freezing point is lowered when we add solutes to a solution. We already
know that in order to freeze a liquid, we have to lower the temperature. As the temperature lowers, the solution
becomes more ordered as it moves toward the solid phase. If we have to lower the temperature to a certain point
to freeze a pure solvent, when we add a solute we add to the entropy of the system. The mixture is more
disordered than the pure. This additional amount of entropy (lack of order or predictability; gradual decline into
disorder) must now be overcome to allow the liquid to change phases into a solid (become ordered). This means
that the temperature will have to be even lower than before. Thus addition of any type of solute to a solvent will
lower its freezing point.
As with boiling point elevation, the equation to figure out how great the change in temperature will be is given
by:

DT = iKfm

DT= change in temperature

i = the van't Hoff factor, which is the number of particles into which the solute dissociates
m = the molality, which is the moles of solute per kilograms of solvent
Kf = the molal freezing point constant (for water, Kf = -1.86 oC/m)

4) Osmosis and Osmotic Pressure

You may have observed raw mangoes shriveling when placed in salt water or wilted flowers reviving when placed
in fresh water. This happens due to a process called osmosis. Osmosis is the flow of solvent molecules from pure
solvent to the solution through a membrane. The flow continues until equilibrium is reached.
The process of osmosis occurs through a membrane that looks continuous but contains small pores that allow small
solvent molecules like water to pass through, but not bigger solute molecules. Such membranes are
called semipermeable membranes (SPM).
The flow of solvent towards the solution side across the semipermeable membrane can be stopped by applying
extra pressure on the solution. This pressure is known as the osmotic pressure of the solution.
Few important things to note –
 During osmosis, the solvent flows from the dilute (lower concentration) to concentrated (high concentration)
side across the semipermeable membrane.
 Osmotic pressure depends on the concentration of the solution.
The osmotic pressure of a solution is the excess pressure applied to the solution to prevent osmosis. It is also a
colligative property and depends on the number of solute molecules and not their identity.
For dilute solutions, osmotic pressure is directly proportional to the molarity (C) of the solution at a given
temperature (T).
Π = C R T = (n2/V) R T
where, Π – osmotic pressure, C – molarity, R – gas constant, T – temperature, V – a volume of solution in liters, n
– the number of moles of solute.
Since n2 = w2/M2, then Π V = w2RT/M2 OR M2= w2RT/Π V
NOTE: The measurement of osmotic pressure is widely used to determine the molar masses of polymers, proteins,
and other macromolecules.

DISTRIBUTION (D) / PARTITION-COEFFICIENT (P) CO-EFFICIENT AND ITS APPLICATIONS

IN PHARMACY:
It is the ratio of concentrations of a compound in a mixture of two immiscible phases at equilibrium. This ratio
is therefore a measure of the difference in solubility of the compound in these two phases. The partition-
coefficient generally refers to the concentration ratio of un-ionized species of compound whereas the
distribution-coefficient refers to the concentration ratio of all species of the compound (ionized plus un-
ionized).
In the chemical and pharmaceutical sciences, both phases usually are solvents. Most commonly, one of the
solvents is water while the second is hydrophobic such as 1-octanol. Hence the partition coefficient measures
how hydrophilic ("water-loving") or hydrophobic ("water-fearing") a chemical substance is. Partition
coefficients are useful in estimating the distribution of drugs within the body. Hydrophobic drugs with high
octanol/water partition coefficients are mainly distributed to hydrophobic areas such as lipid bilayers of cells.
Conversely hydrophilic drugs (low octanol/water partition coefficients) are found primarily in aqueous regions
such as blood serum.
The distribution coefficient (D) of a drug is given as

The partition coefficient (P) of a drug is

Applications
Pharmacology
A drug's distribution coefficient strongly affects how easily the drug can reach its intended target in the body,
how strong an effect it will have once it reaches its target, and how long it will remain in the body in an active
form. Hence, the log P of a molecule is one criterion used in decision-making by medicinal chemists in pre-
clinical drug discovery, for example, in the assessment of drug likeness of drug candidates. Likewise, it is used
to calculate lipophilic efficiency in evaluating the quality of research compounds, where the efficiency for a
compound is defined as its potency, via measured values of pIC50 or pEC50, minus its value of log P.
Pharmacokinetics
In the context of pharmacokinetics (what the body does to a drug), the distribution coefficient has a strong
influence on ADME properties of the drug. Hence the hydrophobicity of a compound (as measured by its
distribution coefficient) is a major determinant of how drug-like it is. More specifically, for a drug to be orally
absorbed, it normally must first pass through lipid bilayers in the intestinal epithelium (a process known
as transcellular transport). For efficient transport, the drug must be hydrophobic enough to partition into the
lipid bilayer, but not so hydrophobic, that once it is in the bilayer, it will not partition out again. Likewise,
hydrophobicity plays a major role in determining where drugs are distributed within the body after absorption
and as a consequence in how rapidly they are metabolized and excreted.
Pharmacodynamics
In the context of pharmacodynamics (what a drug does to the body), the hydrophobic effect is the major driving
force for the binding of drugs to their receptor targets. On the other hand, hydrophobic drugs tend to be more
toxic because they, in general, are retained longer, have a wider distribution within the body (e.g., intracellular),
are somewhat less selective in their binding to proteins, and finally are often extensively metabolized. In some
cases the metabolites may be chemically reactive. Hence it is advisable to make the drug as hydrophilic as
possible while it still retains adequate binding affinity to the therapeutic protein target. For cases where a drug
reaches its target locations through passive mechanisms (i.e., diffusion through membranes), the ideal
distribution coefficient for the drug is typically intermediate in value (neither too lipophilic, nor too
hydrophilic); in cases where molecules reach their targets otherwise, no such generalization applies.

Measurement
A number of methods of measuring distribution coefficients have been developed,
 HPLC-based
 pH-Metric
 Electrochemical
Shake flask-type: The classical and most reliable method of log P determination is the shake-flask method,
which consists of dissolving some of the solute in question in a volume of octanol and water, then measuring
the concentration of the solute in each solvent. The most common method of measuring the distribution of the
solute is by UV/VIS spectroscopy