MODULE: PHARMACEUTICAL SCIENCES & THE

PRACTICE OF PHARMACY

CHAPTER ONE: DISSOLUTION & SOLUBILITY

SEMESTER: ONE

Date of session: 04.11.24 Kenza MANSOURI

Contents:

1. Introduction
2. Definition of terms: Solution, solubility and dissolution
3. Process of dissolution
4. Dissolution rates of solids in liquids
5. Solubility
6. Summary
INTRODUCTION:

v Solutions are encountered frequently in pharmaceutical development, either as a dosage form in

their own right or as clinical trials material.

v Additionally, almost all drugs function in solution in the body.

v We will discuss the principles underlying the formation of solutions from a solute and a solvent
and the factors that affect the rate and extent of the dissolution process.

v This process will be discussed particularly in the context of a solid dissolving in a liquid as this is
the situation most likely to be encountered in the formation of a drug solution, either during
manufacturing or during drug delivery.
v Dissolution of gases in liquids, solids in semisolids, liquids in semisolids and liquids in liquids is
also encountered pharmaceutically.
Definition of terms: Solution, solubility and dissolution:

v A solution may be defined as a mixture of two or more components that form a single phase
which is homogeneous down to the molecular level.

v 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.

v The other components are termed solutes, and these are dispersed as molecules or ions
throughout the solvent, i.e. they are said to be dissolved in the solvent.

v The transfer of molecules or ions from a solid state into solution is known as dissolution.

v Fundamentally, this process is controlled by the relative affinity between the molecules of the
solid substance and those of the solvent.
v 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.

v The solubility of a substance is the amount of it that has passed into solution when equilibrium is
established between the solute in solution and the excess (undissolved) substance.

v The solution that is obtained under these conditions is said to be saturated.

v A solution with a concentration less than that at equilibrium is said to be subsaturated.

v Solutions with a concentration greater than that at equilibrium can be obtained in certain
conditions; these are known as supersaturated solutions.
Unsaturated, saturated & supersaturated solution:

v A saturated solution is a solution that contains the maximum amount of solute that is capable of
being dissolved. For example, at 20oC, the maximum amount of NaCl that will dissolve in 100g of
water is 36g. When 40g is added to H2O, 36g will dissolve and 4g remains undissolved leading to a
supersaturated solution.
v In an unsaturated solution, more solute can be added and dissolved.
v In a supersaturated solution, any added solute will not be dissolved and lead to crystal formation.
v 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.

v However, when the two components forming a solution are either both gases or both liquids,
then it is more usual to use the term miscibility rather than solubility (other than the name, all
principles are the same).

v The rate of solution (dissolution rate) and the amount which can be dissolved (solubility) are not
the same and are not necessarily related.

v In practice, high drug solubility is usually associated with a high dissolution rate, but there are
exceptions; an example is the commonly used film-coating material hydroxypropyl
methylcellulose (HPMC), which is very water soluble yet takes many hours to hydrate and dissolve
in water.
Dissolution mechanisms:

v Assumption: solid crystalline materials, whether drugs or excipients, will dissolve in a similar
manner.

v The dissolution of a solid in a liquid may be regarded as being composed of two consecutive
stages.

1. First is an interfacial reaction that results in the liberation of solute molecules from the solid
phase to the liquid phase. This involves a phase change so that molecules of the solid become
molecules of the solute in the solvent in which the crystal is dissolving.

2. After this, the solute molecules must migrate through the boundary layer surrounding the
crystal to the bulk of solution (diffusion through boundary layer).
1. Interfacial reaction:

i. Leaving the surface. Dissolution involves the replacement of crystal molecules by solvent
molecules.

v The process of the removal of drug molecules from a solid, and their replacement by solvent
molecules, is determined by the relative affinity of the various molecules involved.
v The solvent/solute forces of attraction must overcome the cohesive forces of attraction between
the molecules of the solid.
ii. Moving into the liquid. On leaving the solid surface, the drug molecule must become
incorporated in the liquid phase, i.e. within the solvent.

v Liquids are thought to contain a small amount of so-called free volume.

v This can be considered to be in the form of ‘holes’ that, at a given instant, are not occupied by the
solvent molecules themselves. Individual solute molecules are thought to occupy these holes,
2. Diffusion through the boundary layer:

v This step involves transport of the drug molecules away from the solid–liquid interface into the
bulk of the liquid phase under the influence of diffusion or convection.

v Boundary layers are static or slow- moving layers of liquid that surround all solid surfaces that are
surrounded by liquid.

v Mass transfer occurs more slowly by diffusion through these static or slow-moving layers.

v These layers inhibit the movement of solute molecules from the surface of the solid to the bulk of
the solution.

v The solution adjacent to the solid will be saturated (because it is in direct contact with
undissolved solid).
v During diffusion, the solution in the boundary layer changes from being saturated (C S) at
the crystal surface to having a concentration equal to that of the bulk of the solution (C) at its
outermost limit.
Energy/work changes during dissolution:

v Gibbs free energy (G) is the energy associated with a chemical reaction that is available to work.
The Gibbs free energy determines whether of not a reaction is favourable or not (spontaneous).

ΔG = ΔH - TΔS
ΔG= the change of free energy
ΔH= the change in enthalpy (internal energy)
T= thermodynamic temperature (in Kelvins)
ΔS= change in entropy (measurement of degree of randomness, i.e. how energy is
distributed within system)

v ΔG < 0 The reaction is spontaneous

v ΔG> 0 the reaction is non spontaneous
v ΔG=0 the reaction is at equilibrium
v In most cases heat is absorbed when dissolution occurs, and the process is usually defined as an
endothermic one and the solution often cool (e.g. table salt in water)

v In some systems, where there is marked affinity between solute and solvent, the process is an
exothermic one and heat may be evolved (gas in liquid).
Dissolution rates of solids in liquids :

v Like any reaction that involves consecutive stages, the overall rate of dissolution will be
dependent on which of the steps previously described is the slowest (the rate-determining or
rate-limiting step).

v In dissolution, the interfacial step is almost always virtually instantaneous, and so the rate of
dissolution will most frequently be determined by the rate of the slower step of diffusion of
dissolved solute through the static boundary layer of liquid that exists at a solid–liquid interface.

i. Interface-controlled dissolution rate:

On the rare occasions when the release of the molecule from the solid into solution is slow and the
transport across the boundary layer to the bulk solution is faster, dissolution is said to be interfacially
controlled.
ii. Diffusion-controlled dissolution rate:

v If the rate of diffusion of the solute molecules through the boundary layer is the slowest step,
dissolution is said to be diffusion controlled.

v The movement of solute molecules through the boundary layer will obey Fick’s first law of
diffusion.

v This law states that the rate of change in the concentration of a dissolved material with time is
directly proportional to the concentration difference between the two sides of the diffusion layer:

!"
= 𝑘∆𝐶
!#

C is the concentration of solute in solution at any position and at time t

& constant k is the rate constant
v The energy difference between the two concentration states provides the driving force for the
diffusion.

v ΔC is the difference in the concentration of the solution at the solid surface (C1) and the bulk of
the solution (C2).
Thus ΔC = C1 − C2.

v If C2 is less than saturation, the molecules will move from the solid to the bulk of solution (as
during dissolution).

v If the concentration of the bulk (C2) is greater than saturation, the solution is referred to as being
supersaturated and movement of solid molecules will be in the direction of bulk solution to the
surface (as occurs during crystallization).
iii. Noyes–Whitney equation:

v The Noyes–Whitney equation was developed to define the dissolution from a single spherical
particle.

v This equation is used to predict or estimate the dissolution rate of pharmaceutical particles.

v The rate of mass transfer of solute molecules or ions through a static diffusion layer (dm/dt) is
directly proportional to the area available for molecular or ionic migration (A) and the
concentration difference (ΔC) across the boundary layer and is inversely proportional to the
thickness of the boundary layer (h).

𝑑𝑚 𝐷𝐴∆𝐶
=
𝑑𝑡 ℎ

D= diffusion coefficient (m-2s-1)

Solubility:

Understanding the phenomenon of solubility helps the pharmacist to:

v Select the best solvent for a drug or a mixture of drugs.

v Overcome problems arising during preparation of pharmaceutical solutions.

v Many drugs are formulated as solutions, or added as powder or solution forms to liquids.

v Drugs with low aqueous solubility often present problems related to their formulation and
bioavailability.
Solubility:

v The solution produced when equilibrium is established between undissolved and dissolved solute
in a dissolution process is termed a saturated solution.

v The amount of substance that passes into solution in order to establish this equilibrium at
constant temperature and so produce a saturated solution is known as the solubility of the
substance.

v It is possible to obtain supersaturated solutions but these are unstable and precipitation of the
excess solute tends to occur readily and spontaneously.

v Solubility is expressed in terms of the maximum mass or volume of solute that will dissolve in a
given mass or volume of solvent at a particular temperature and at equilibrium.
Solubility:

v In a quantitative way: it is the concentration of solute in a saturated solution at a certain

temperature.

v In a qualitative way: it is the spontaneous interaction of two or more substances (solute &
solvent) to form a homogeneous molecular dispersion.
Types of solutions:
State of solvent State of solute State of solution Examples
Gas Gas Gas Air, natural gas
Liquid Liquid Liquid Alcoholic drinks,
antifreeze solution
Liquid Solid Liquid Seawater, sugar
solution
Liquid Gas Liquid Carbonated soda,
ammonia solution
Solid Solid Solid Metal alloys: brass,
bronze
Solid Gas Solid Hydrogen in
platinum
Solubility curve:

Any solution can be made saturated, unsaturated, or supersaturated by changing the temperature.
Thermodynamic solubility of drugs:

v The thermodynamic solubility of a drug in a solvent is the maximum amount of the most stable
crystalline form that remains in solution in a given volume of the solvent at a given temperature
and pressure under equilibrium conditions.

v The equilibrium involves a balance of the energy of three interactions against each other:
• Solvent with solvent
• Solute with solute
• Solvent and solute
Steps of solid going into solution:

Steps of solid going into solution.

v Step 1: Hole open in the solvent
v Step 2: One molecule of the solid breaks away from the bulk
v Step 3: The solid molecule enter into the hole in the solvent
Solubility process:

A mechanistic perspective of solubilization process for organic solute in water involves the
following steps:
• Break up of solute-solute intermolecular bonds
• Break up of solvent-solvent intermolecular bonds
• Formation of cavity in solvent phase large enough to accommodate solute molecule
• Transfer of solute into the cavity of solvent phase
• Formation of solute-solvent intermolecular bonds
Solubility expression:
Solubility expressions:

v The USP lists the solubility of drugs as: the number of ml of solvent in which 1g of solute will
dissolve.
e.g. 1g of boric acid dissolves in 18 mL of water, and in 4 mL of glycerin.

v Substances whose solubility values are not known are described by the following terms:
Biopharmaceutics Classification System (BCS):

v BCS is a scientific framework for classifying Drug substances according to their aqueous solubility
and their intestinal permeability.

v A drug is considered highly soluble when highest strength is soluble in 250ml or less of aqueous
media within pH 1-1,6 at 37oC.

v A drug is considered highly permeable when the systemic bioavailability or extent of absorption in
humans is determined to be at least 85% or more of an administered dose in comparison to an
intravenous reference dose.
Three types of interaction in the solution making process:

1. solvent – solvent interaction (separating the solute)

2. solute – solute interaction (overcoming intermolecular forces)
3. solvent - solute interaction (polar attractions)
Solvent-Solute Interactions:

v In pre - or early formulation, selection of the most suitable solvent is based on the principle of
“like dissolves like”.

v That is, a solute dissolves best in a solvent with similar chemical properties and two substances
with similar intermolecular forces are likely to be soluble in each others.

v Polar solutes dissolve in polar solvents, e.g. salts & sugar dissolve in water .

v Non polar solutes dissolve in non polar solvents, e.g. naphthalene dissolves in benzene.
Polar Solute-Polar Solvent:

Ammonia Dissolves in Water:

v Polar ammonia molecules dissolve in polar water molecules.
v These molecules mix readily because both types of molecules engage in hydrogen bonding.
v Since the intermolecular attractions are roughly equal, the molecules can break away from each
other and form new solute (NH3) - solvent (H2O) hydrogen bonds.
Solute-Solvent interactions:

v If the solvent is A & the solute is B, and the forces of attraction are represented by A-A, B-B and
A-B, one of the following conditions will occur:

v If A-A >> A-B The solvent molecules will be attracted to each other & the solute will be excluded.
Example: Benzene & water, where benzene molecules are unable to penetrate the closely bound
water aggregates.

v If B-B >> A-A The solvent will not be able to break the binding forces between solute molecules.
Example NaCl in benzene, where the NaCl crystal is held by strong electrovalent forces which
cannot be broken by benzene.

v If A-B >> A-A or B-B, or the three forces are equal The solute will form a solution. Example: NaCl
in water.
Mode of action of ‘Like dissolves like’:

Nature of solvent Mechanism of solubility Example

Polar v High dielectric constant Water + ethanol

v H-bond formation
v Dipole interaction
Non polar Weak Van Der Waal’s forces Fats, oils, alkaloidal
bases + CCl4
Semi polar Induce certain degree of Acetone increases
polarity solubility of ether
in water
v The solubility of a substance also depends on structural features such as the ratio of the polar to
the non-polar groups of the molecule.

v As the length of a nonpolar chain of an aliphatic alcohol increases, the solubility of the compound
in water decreases.

v Straight-chain monohydroxy alcohols, aldehydes, ketones, and acids with more than four or five
carbons cannot enter into the hydrogen- bonded structure of water and hence are only slightly
soluble.

v When additional polar groups are present in the molecule, as found in propylene glycol
(CH₃CHCH₂OH), glycerin, and tartaric acid, water solubility
Non polar solvents:

v Non-polar solvents are unable to reduce the attraction between the ions of strong and weak
electrolytes because of the solvents' low dielectric constants.

v They are unable to form hydrogen bonds with non electrolytes.

v Non polar solvents can dissolve non polar solutes through weak van der Waals forces.
Example: solutions of oils & fats in carbon tetrachloride or benzene. Polyethylene glycol 400 , Castor
oil.

v London Van Der Waals forces are intermolecular forces found between all molecules. The
stronger the intermolecular forces, the greater the melting and boiling points and viscosity will
be.
Types of solutions:

Solutions of pharmaceutical importance include:

v Gases in liquids
v Liquids in liquids
v Solids in liquids
Solubility of gases in liquids:

v The solubility of a gas in a liquid is the concentration of the dissolved gas when it is in equilibrium
with some of the pure gas above the solution.
v When the pressure above the solution is released (decreases), the solubility of the gas decreases
v As the temperature increases the solubility of gases decreases.
v The solubility depends on the pressure, temperature, presence of salts and chemical reactions.

v Henry’s law= Solubility is directly proportional to partial pressure of gas at a constant

temperature.
S= k.P
S=C= concentration of dissolved gas (mol/L)
K= Henry’s law proportionality constant (specific to solute, solvent and temperature)
P= Partial pressure of the gaseous solute above the solution
Solubility of liquid in liquid:

v Preparation of pharmaceutical solutions involves mixing of 2 or more liquids:

- Alcohol & water to form hydroalcoholic solutions
- Volatile oils & water to form aromatic waters
- Volatile oils & alcohols to form spirits , elixirs

v Liquid-liquid systems may be divided into 2 categories:

- Systems showing complete miscibility such as alcohol and water. The components of an ideal
solutions are miscible in all proportions.

- Systems showing partial miscibility as phenol and water; two liquid layers are formed each
containing some of the other liquid in the dissolved state.

v The term miscibility refers to the mutual solubility of the components in liquid liquid system.
Solubility of liquid in liquid :

v Partial miscibility results when one of the components tends to self-associate because the
attractions between its own molecules are greater than those between its molecules and those of
the other component.

v The extent of the reduction in miscibility depends on the strength of the self-association and,
therefore, on the degree of deviation from Raoult’s law.

v In those cases where partial miscibility occurs under normal conditions, the degree of miscibility
is usually dependent on the temperature.
v Virtual immiscibility may be exhibited when the self-association is very strong and the positive
deviation from Raoult’s law is large.
Raoult’s law:

v An understanding of many of the properties of solutions requires an appreciation of the concept

of an ideal solution and its use as a reference system, to which the behaviours of real (nonideal)
solutions can be compared. This concept is itself based on a consideration of vapour pressure.

v All condensed systems have the inherent ability to give rise to a vapour pressure. However, the
vapour pressures exerted by solids are usually much lower than those exerted by liquids, because
the intermolecular forces in solids are stronger than those in liquids. Thus the escaping tendency
for surface molecules is higher in liquids.

v For a mixture of 2 substances Raoult’s law tells us that a solvent's partial vapour pressure
in a solution (or mixture) is equal to the vapour pressure of the pure solvent multiplied
by its mole fraction in the solution.
 Psolution = Xsolvent . Psolvent
Psolution = vapour pressure of solution
Psolvent = vapour pressure of a solvent
Xsolvent = mole fraction of solvent (moles of solvent divided by total amount of moles of solvent and solute)
Ideal solution & Raoult’s law:

v The concept of an ideal solution has been introduced in order to provide a model system that can
be used as a standard with which real or nonideal solutions can be compared.

v It is assumed that the strengths of all intermolecular forces are identical. Thus solvent–solvent,
solute–solvent and solute–solute interactions are the same and are equal to the strength of the
intermolecular interactions in either the pure solvent or the pure solute.

v Therefore, an ideal solution is one in which there is no change in the properties of the
components, other than dilution. It is said that ideal solutions obey Raoult’s law.

v Such behaviour is expected to be exhibited only by real systems composed of chemically similar
components, because it is only in such systems that the condition of equal intermolecular forces
between components (e.g. Benzene & Toluene).
Real solutions:

v In real solutions the "cohesive“ force of attraction between A for A exceeds the "adhesive" force
of attraction existing between A and B.

v Alternatively, the attractive forces between A and B may be greater than those between A and A
or B and B. This may occur even though the liquids form solution in all proportions. Such mixtures
are real or non-ideal.
Raoult’s law deviations:

v Positive deviation: P> Xa P

v This occurs in systems showing an increase in miscibility with rise in temperature.

v The positive deviation arises from a difference in the cohesive forces that exist between the
molecules of each component in a liquid mixture.

v The interaction between A and B molecules is less than that between molecules of the pure
constituents (A-A or B-B), the presence of B molecules reduces the interaction of the A-A
molecules correspondingly reduce the B- B interaction.
Raoult’s law deviations:

v Negative deviation: P< Xa P

v This is the case in systems that show a decrease in miscibility with rise in temperature.

v Only few mixtures exhibit a lower critical solution temperature (CST), e.g. triethylamine & water
or chloroform & acetone.

v In such systems, miscibility increases as the temperature falls.

v This happens when the "adhesive" attractions between molecules of different species exceed the
"cohesive" attractions between like molecules, the vapor pressure of the solution is less than that
expected from Raoult's ideal solution law.
Raoult’s law deviation:

v Some systems showing upper and lower critical

solution temperatures
v The decrease in miscibility with increase in
temperature in systems having a lower CST is not
indefinite.
v Above a certain temperature, positive deviations
from Raoult’s law become important and
miscibility starts to increase again with further rise
in temperature.
v This behaviour is shown by the nicotine–water
system.
Factors affecting solubility of solid in liquid:

v Temperature
v Nature of solvent ( like dissolves like)
v Pressure
v pH
v Particle size
v Crystal structure
v Molecular structure
v Solute - solvent interactions
v Addition of substituent
v Common ion effect
v Solubilizing agent
Molecular structure:

v Slight modification in the molecular structure of solids may lead to marked changes in their
solubility in the given solvent. For example, if a weak acid ( CH COOH →weak electrolyte, poorly
soluble) is converted into its salt (CH3COONa), its ionic dissociation in water increases markedly
leading to an increase in the interaction between the solute and the solvent which ultimately
leads to an increase in the solubility.

v Solubility can also be decreased by modifications such as esterification.

Chloramphenicol (antibiotic) -----------------------→ Chloramphenicol palmitate
Soluble Poor Soluble

Such a decrease in solubility is sometimes beneficial in pharmaceutical practice since this decrease in
solubility helps in taste masking of certain drugs such as chloramphenicol (very bitter) to
chloramphenicol palmitate (tasteless).
v Solubility of the drug is directly affected by the chemical groups attached to the
molecule.

Hydrophilic groups such as OH, COO- and NH3+ (hydroxide, carboxyl, ammonia) will increases
solubility of the drug compared to hydrophobic groups such as methyl, ethyl, ethoxy or chlorine (CH3,
CH3CH2, OCH2CH3, Cl)
Melting point:

v Solubility of chemical agents is inversely related to their melting point.

v As the melting point of the drug is increased, the solubility would be expected to decrease.

v Melting point is the temperature at which a given solid material changes from a solid state to a
liquid, or melts.

v Fortunately, the melting points of majority of the APIs and excipients for solid oral formulations
are well above the typical operating temperature range for testing, 40–80°C.

v However, care must be taken when dealing with drugs with relatively low melting point or when
excipients with relatively low melting points are included in a solid formulation.
v It is also important to note that when such API or excipient is mixed into a solid formulation, the
actual melting point of the API or excipient in the formulation can be even lower than that of the
pure API or excipient due to the so called melting point depression; therefore, a safety margin
should be considered.

v Melting point determination is an important tool to determine the purity of a substance and its
solubility.
Common ion effect:

v The common ion effect is an effect that suppresses the ionization of an electrolyte of a weak acid
(or base) when another electrolyte (which contains an ion which is also present in the first
electrolyte, i.e. a common ion) is added. This leads to a reduction of solubility.

v Example: Silver Chloride AgCl

AgCl(s) Ag+(aq) + Cl-(aq)

If NaCl is added, the equilibrium will shift to the left and some AgCl will precipitate, which will reduce
solubility.
Effect of surfactants :

v Surfactants are also known as solubilising agent (surface active agents).

v Solubility of poor soluble drugs may be enhanced by a technique known as micellar solubilisation,
which involves the use of surfactants for increasing the solubility. Poorly water-soluble drugs can
be solubilized in micelles to enhance their aqueous solubility.

v When a surfactant having a hydrophilic and a lipophilic portion is added to a liquid, it rearranges
itself to from a spherical aggregate known as micelle.
v In aqueous medium, the surfactant molecule orientate in such a manner that their hydrophilic
portion faces the water and the lipophilic portion resides in the micellar interior. An insoluble
compound added to the surfactant liquid, enters the micelle interior and gets solubilised.
Buffer solutions and buffer capacity:

v A buffer solution resists changes in pH upon dilution or addition of small amount of acid or base.
However, pH of buffer solution can change if large amount of strong acid (or base) are added.
v There are 2 types of buffer solutions: acidic or basic buffer.
v Buffer capacity of the measure of the resistance of a buffer solution to pH change on addition of
hydroxide ions (OH-).
v Buffer solutions are prepared by controlling the ratio of salt- acid (or salt base ratio) using the
known pKa value (& Hasselbalch Henderson) when mixing the weak acids to their conjugate
bases.
v Buffer solutions are widely used to enhance solubility, stability and to optimise therapeutic effect
of the drug.
v They are also used in parenteral preparation (pH 7.4) and to prevent tissue irritations (eye drops)
Colligative properties of solutions:

v When a non-volatile solute is dissolved in a solvent, certain properties of the resultant solution
are largely independent of the nature of the solute and are determined by the concentration of
solute particles. These properties are known as colligative properties (Greek: collected together).

v The most important colligative property from a pharmaceutical aspect is osmotic pressure.

v However, since all colligative properties are related to each other by virtue of their common
dependency on the concentration of the solute molecules, other colligative properties (which
include lowering of the vapour pressure of the solvent, elevation of its boiling point and
depression of its freezing point) are of pharmaceutical interest.
SUMMARY:

v Dissolution rate and solubility are two separate properties. While a solid with a fast dissolution
rate often has a high solubility (and vice versa), this is not always the case.

v The process of dissolution involves a molecule, ion or atom of a solid entering a liquid phase in
which the solid is immersed.

v The rate of dissolution is controlled either by the speed of removal of the molecule, ion or atom
from the solid surface or by the rate of diffusion of that moiety through a boundary layer that
surrounds the solid.
v Various factors influence the rate of diffusion of a solute through a boundary layer.

v Some of these may be manipulated by the formulator.

v It is important for the formulator to be aware of the parameters which affect the solubility of a
solid in a liquid phase.

v The dissolution rate and solubility of solids in liquids, gases in liquids and liquids in liquids are
each important in pharmaceutical science.