CYPRUS INTERNATIONAL UNIVERSITY
2024-2025 FALL SEMESTER
PHAR 217
Introduction to Pharmaceutical Technology
SOLUTION, SOLUBILITY AND DISSOLUTION
Lecture 2: (11.10.2024)
Solution
• Solutions is a mixture of one or more component ,either
as a dosage form itself or clinical trials material.
Additionally, almost all drugs function in solution in the
body.
• A solution is a homogenous molecular dispersion that
consist of a solvent and the solute which dissolves in it
e.g. sodium chloride in water. The component that
determines the phase of the solution is termed the
solvent.
• The other components 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: dissolving salt in water, salt is the solute
Dissolution VS Solubility
The transfer of molecules or ions from a solid state into solution
is known as dissolution. This process is controlled by the
relative affinity between the molecules of the solid
substance and those of the solvent (Dissolution is process of
dissolving solutes in a solvent).
Solubility of a solute in a solvent is defined as the extent
to which a solute dissolves in a solvent until equilibrium is
reached between the solute in solution and the excess
undissolved solute.
The solution that is obtained under these conditions is said
to be saturated.
Solution Formation Vocabulary
• Soluble: a substance that dissolves in a solvent
• Insoluble: a substance that does not dissolve in a solvent
• Solubility: The maximum amount of solute that will dissolve in a given amount of
solvent at a specified temperature and pressure (Solubility often expressed in g/100
mL.) E.g. 0.30 g of I2 dissolved in 1000 g of H2O
• 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
subsaturated. Solutions with a concentration greater than
equilibrium can be obtained in certain conditions, These are known as
supersaturated solutions.
• Saturation Solubility (Saturation Concentration) is the maximum amount of an
active substance that can dissolve under normal conditions at a certain temperature.
If this value is increased by adding other substances or due to other factors (such as
temperature) then a super-saturated solution is prepared.
Methods of expressing solubility
Quantity per quantity: Weight of solute contained in a given
volume of solution
Parts: No of parts of solute dissolved in no of parts of solvent
◦Parts by weight in parts by volume
◦Parts by volume in parts by volume of the final solution
Percentage: % w/v, %v/v, % w/w
Molarity: No of moles of solute contained in one liter of solution
Molality: Number of moles of solute in 1kg of solvent
Mole fraction: No of moles of solute divided by the total number
of moles of solute
and solvent
Determination of Solubility
Determination of Solubility
Concentrated Vs dilute solution
• What is the difference between concentrated & diluted
solutions???
TYPES OF SOLUTION
Since there are three states of matter i.e. solid, liquid and gas, nine different types
of solution with two components are possible.
SOLUTE SOLVENT
Gas Gas
liquid Gas
Solid gas
Gas Liquid
Liquid Liquid
Solid Liquid
Gas Solid
Liquid Solid
Solid Solid
DETERMINATION OF THE SOLUBILITY OF SOLIDS IN LIQUIDS
The following points should be observed in all solubility determinations
1. The solvent and solute must be pure
2. A saturated solution must be obtained before any solution is removed
for analysis
3. The method of separating a sample of saturated solution from
undissolved solute must be satisfactory
4. The method of analyzing the solution must be reliable
5. Temperature must be adequately controlled.
FACTORS AFFECTING THE SOLUBILITY OF SOLIDS IN LIQUIDS
1. Temperature: in most cases, the dissolution
of a solid in a liquid involves the absorption of
heat, i.e. it is an endothermic process with a positive
heat of solution. If this type of system is heated, it
will tend to react in a way that will nullify the
constraint imposed upon it i.e. the rise in
temperature.
Thus, a rise in temperature will lead to an increase in
the solubility of a solid with a positive heat of
solution.
Conversely, if the dissolution of a solid involves the
liberation of heat,i.e. it is an exothermic process with
a negative heat of solution, then an increase in
temperature will lead to a decrease in solubility.
FACTORS AFFECTING THE SOLUBILITY OF SOLIDS IN LIQUIDS
2. Particle size of the solid: The solubility of a substance will increase with a decrease in
particle size.
3. PH: Ph can affect solubility for solutes that are weak acids or bases. For instance, increasing
the pH can increase the solubility of acidic solutes (by deprotonation), while lowering the pH
can increase the solubility of basic solutes (by protonation).
4. Agitation or Stirring: Stirring or shaking can increase the rate of solubility. This helps
distribute the solute particles throughout the solvent and brings fresh solvent molecules into
contact with the solute, speeding up the dissolution process.
Additional Substances
• 1. Additional Substances
(a) Common ion effect: The solubility of a sparingly soluble electrolyte is decreased by
the addition of a second electrolyte that possesses a similar ion to the first.
(b) Use of various techniques. Such as- micro-nization or solid dispersion
Stability
•The stability of a drug (and of formulation excipients) is critically
important to ensure that the patient receives the correct dose of the
active ingredient.
•For drugs that can degrade to produce toxic materials, it is essential to
determine the conditions under which this might occur so as to find
methods of prevention or stabilisation and/or to determine limitations in
terms of shelf life and storage conditions.
•Solid phase stability depends on several factors:
• temperature
• pH
• humidity
• hydrolysis
• oxidation
Water solubility of non-electrolyte either decrease or increase by
addition of electrolyte
• Solubility of electrolyte increases-----→
SALTING IN
• Solubility of electrolyte decreases---→
Salting out
DISSOLUTION RATES
• The dissolution of a solid in a liquid involves the transfer of mass from a solid to
a liquid phase. The overall transfer process may be regarded as being composed of
two consecutive stages.
• The first of these, which is and interfacial reaction that results in the liberation
of solute molecules from the solid phase, is followed by the transport of solute
away from the interfacial boundary under the influence of diffusion or
convection.
• The Noyes-Whitney equation is commonly used to describe the dissolution rate of
a solute:
• dC=DA(Cs−C)
Dt h
The general criteria for selection of the solvent :
1. The more nearly solvents & solutes are alike structurally, the more rapidly solution takes place.
2. Polar liquids dissolve the electrovalent compounds, but they are poor solvent for non polar
substances, (meanwhile, the non polar liquids dissolve the non polar or slightly polar solutes).
In addition, polar liquids should be miscible with other polar liquids & vise versa.
3. Complex organic compounds which have polar & non polar groups in their molecules may
dissolve in polar liquids, but their solubility tends to decrease in proportion to the number of non
polar groups.
4. Semipolar liquids, such as ethyl alcohol, possess some of the properties of both polar &
non polar solvents.
FACTORS AFFECTING THE RATE OF DISSOLUTION
1. Temperature: Le Chatelier’s principle will apply to the process of
dissolution. An increase in temperature will increase the solubility of a solid with a
positive heat of solution.
2. Agitation (Stirring): This will help to increase the dissolution rate by
reducing the thickness of the diffusion pathway.
3. Surface Area: Dissolution rate is increased by an increase the in the surface area of
the solid. Reduction in the particle size results in an increase in surface area.
4. Polymorphism: A substance is said to exhibit polymorphism if it can exist in
more than one type of structure, which may be stable or metastable.
Polymorphism in solids give rise to a difference in crystalline form between
polymorphs of the same substance. This difference may produce a change in the
dissolution rates of the polymorphs.
FACTORS AFFECTING THE RATE OF DISSOLUTION
• Viscosity: An increase in viscosity of the liquid phase will reduce the rate of
diffusion of the solutes thereby reducing the dissolution rate.
• Molecular structure of solute: Factors such as the use of salts of either weakly
acidic or weakly basic drugs or esterification of neutral compounds can increase
solubility and dissolution rate
• Nature of the dissolution medium: Factors such as solubility
parameters, pH and presence of cosolvents will affect the rate of dissolution.
• Crystalline form of solid: the presence of polymorphs, hydrates,
solvates or the amorphous form of the drug can all have an influence on the
dissolution rate.
• Presence of other compounds: The common ion effect, complex formation and
the presence of solubilizing agents can affect the rate of dissolution.
• Volume of the dissolution medium: The higher the volume of the
dissolution medium, the higher the rate of dissolution until the solution
becomes saturated and the rate of dissolution will reduce unless the is a
process to add a fresh dissolution medium or remove dissolved solutes from
the medium (sink condition).
• Any process that removes dissolved solute from the dissolution
medium will increase the rate of dissolution.
• Thickness of the boundary layer: The higher the thickness of the
boundary layer, the lower the rate of dissolution.
• Diffusion coefficient of solute in the dissolution medium.
• Diffusion Layer Thickness (Noyes-Whitney Equation)
According to the Noyes-Whitney equation, the dissolution rate is inversely proportional to the
thickness of the stagnant layer (diffusion layer) surrounding the solute. Agitation, temperature, and
other factors can reduce this layer's thickness, increasing the dissolution rate.
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