SOLUTION

DR NGOZI UDEM
 Pharmaceutical solution
• Pharmaceutical solutions are homogenous
mixtures of one or more solutes dispersed
molecularly in a dissolving medium( solvent).
• Comprise the medicinal agent in a solvent and
most of times with additional agents.
• A drug dissolved in an aqueous solution is in
the most bioavailable and consistent form.
• Because the drug is already in solution no
dissolution step is necessary before systemic
absorption occurs.
 solubility
• The saturated solution of a chemical in a solvent
is the maximum concentrations of a solution
which may be prepared at a given temperature.
This is usually called solubility.
• Solubility for medicinal agents in a given solvent
are given in British Pharmacopeia and Martindale.
• Solubility are usually stated as the number of
parts of solvent (by volume) that will dissolve one
part (by weight or volume) of the substance
 Solubility Contd
• Example of solutes
• Diazepam solubility
• Water: 1 in 1000 (which means 1 g of Diazepam will
dissolve in 1000 ml of water)
• Diazepam is very slightly soluble in water.
• Alcohol: 1 in 30 ( 1 g of diazepam dissolves in alcohol
which means is soluble)
• Chloroform : 1 in 10 (1 g of diazepam dissolves in 10
ml of chloroform) Diazepam is freely soluble in
chloroform.
 Factors affecting solubility
• Compounds that are predominantly non-
polar tend to be more in non-polar solvents,
such as chloroform or a vegetable oil.
• Polar compounds tend to be more soluble in
polar solvents such as water and ethanol.
• pH will also affect solubility for many drugs are
weak acids or bases.
 Factors affecting solubility/ POLARITY
• Ionized form of a compound will be the most
water soluble hence a weakly basic drug will be
most soluble in an aqueous solution that is acidic
• Acid or alkali may therefore added to manipulate
solubility.
• most cases solutes dissolve in solvents that have
a similar polarity.
• "Like dissolves like". Non-polar solutes do not
dissolve in polar solvents and the other way
round.
 Temperature
• Solubility increases with temperature for
most solids dissolved in liquid water.
• This is because higher temperatures increase
the vibration or kinetic energy of the solute
molecules.
 MOLECULE SIZE
• The larger the molecules of the solute are, the
larger is their molecular weight and their size.
• It is more difficult for solvent molecules to
surround bigger molecules.
• a general rule can be found that larger
particles are generally less soluble.
• Therefore particle size reduction will increase
the rate of solution
 Stirring increases the speed of dissolving

• Stirring does not have an affect on solubility of

a substance, but only increases the speed of
the solubility process
• it increases move of the solvent of what
exposes solute to fresh portions , thus
enabling solubility.
• As molecules in liquid substances are in
constant move during stirring, the process
would take place at a shorter time.
 Factors affecting the rate of dissolution
• The various factors that affect the in-vitro rate of
diffusion- controlled dissolution of solids in liquids can
be predicted by examination of Noyes-Whitney
equation.
• Dm/dt = K1 A Cs- C/h
• Key ;Dm/dt= rate of mass transfer of solute molecules or ions through static diffusion layer
• A = Area available for molecular or ionic migration
• Cs-C = concentration difference across the boundary layer (Cs is saturated conc in contact with
solid
• h= thickness of the boundary layer
• K= Diffusion coefficient
• C is 0 when the volume of the solvent is large or solute is removed from bulk at a faster rate
• Sink conditions may arise in vivo when a drug is absorbed into the body from its solution in GIT
at a faster rate than it dissolves in those fluids from a solid dosage form
 Factors affecting in vitro dissolution rates of solids in
liquids
Term in Noyes-Whitney Equation Affected by

A:Surface area of undissolved solid Size of solid particles (A increases with particle size
( rate of dissolution increases proportionately with reduction)
increasing A) Dispersibility of powdered solid in dissolution medium)
Porosity of solid particles

Cs: Saturated solubility of solid in dissolution medium Temperature

(rate of dissolution increases proportionally with Nature of dissolution medium
increasing differences between Cs and C. Thus high Cs Molecular structure of solute
speeds up dissolution rate) Crystalline form of solid
Presence of other compounds

C: concentration of solute in solution at time t ( rate of Volme of dissolution medium (increased volume
dissolution increases proportionally with increasing decreases C)
difference between Cs and C, thus low C speeds up Any process that removes dissolved solute from the
dissolution rate) dissolution medium (hence decreasing C)

K: dissolution rate constant Diffusion coefficient D of solutes in the dissolution

medium
viscosity of medium

h: thickness of boundary layer (Rate of Dissolution Degree of agitation of dissolution medium (increased
 Solution of liquids in Liquids
• In the discussion of solutions of liquid in liquids, it
is evident that the distinction between terms
solute and solvent loses its significance.
• In a solution of water and glycerin, which shall be
considered to be the solute or the solvent.

• When two liquids are only partially soluble in each

other, the distinction between solute and solvent
might be reversed easily. Solvent is usually given
to the consistent present in larger quantity.
 Binary Systems
• Types of liquid-pairs recognized as binary
systems
1) Those that are soluble completely in each other
in all proportions. Example: alcohol and water,
glycerin and water, alcohol and that glycerin.
2) Those that are soluble in each other in definite
proportions. E.g phenol and water, nicotine and
water, ether and water.
3) Those that are imperceptible soluble in each
other in any proportion. E.g liquid petrolatum
and water, castor oil and water
 Binary Systems
• On this graph, the area inside the curve represents
the region where the mixtures of phenol and water
will separate into two layers.
• Region outside of the curve, is where homogenous
solution will be obtained.

• The maximum temperature on this curve is called the

critical solution temperature.
• it is temperature above which a homogenous
solution occurs, regardless of the composition of
mixture. The temperature for phenol and water to be
66.8 oC
 Ternary Systems
• Addition of a third liquid to a binary system to
produce a tertiary or three-component system can
result in several possible combinations.
• If the third liquid is soluble in only one of the two
original liquids or if its solubility of the original
liquids is markedly different, the mutual solubility of
the original pair will be decreased.
• That is the upper critical solution temperature will be
increased and a lower critical solution temperature
will be reduced
If the addition of a liquid having roughly the
same solubility in both concentrations of the
original pair will result in an increase in their
mutual solubility.
An upper critical solution temperature then will
be lowered and a lower critical solution
elevated.
• Solutions of liquids: The distribution of
solutes between immiscible liquids.
• Application of the distributions of law in
pharmacy.
 Distribution law:

• According to the distribution law, a solute is

divided between two layers of immiscible
solvents so that the ratio of its concentration
in each solvent equals the ratio of its solubility.
• C1/C2 = K

The constant k is the distribution coefficient,

while C1 and C2 are the molar equilibrium
concentrations.
 Example of Distribution law:

• Finding the equilibrium constant for the equilibrium

is an example of how the distribution law may be
used.
• Solubility Determination: The value of K is equal to
the ratio of solute solubility in the two solvents.
• If we know the value of k and the solute's solubility
in one solvent, we may compute the solute's
solubility in other solvents.
• K = C1/C2 = S1/S2
 Application of the Distribution of law in
Pharmacy
• A solute's solubility can be determined.
• A single substance can be extracted from a
mixture of components with the help of this
law.
• It's employed in high-performance liquid
chromatography
Application of the distributions of law in pharmacy.

• most important application of the distribution law is in

the process of extraction, in the laboratory as well as in
industry.
• In the laboratory, it is frequently used for the removal of a
dissolved organic substance from aqueous solution with
solvents such as benzene, ether, chloroform, carbon
tetrachloride, etc.
• The applications of distribution law in pharmaceutical
analysis states that an immiscible solute is dispersed
between two solvent layers in a manner such that its
solubility is proportional to its absorption in each solvent.