States of Matter
Contents of
This Chapter
• States of matter
• Latent heat of fusion
• Vapour pressure
• Boiling point
• Aerosols-inhalers
• Liquefaction of gases
• Concept of crystalline solids
• Polymorphism
• Amorphous solids
Intended
Learning Objectives
• At the end of this lecture, student will be able to
– Describe the different states of matter
– Discuss the transitions between different states of matter
– Describe the different states of matter
– Discuss the concept of vapour pressure, boiling point and
pharmaceutical aerosols
– Describe the differences in the intra and intermolecular
forces and their relevance to different types of molecules
– Discuss the differences in the strengths of the
intermolecular forces that are responsible for stability of structures in the
different states of matter
– Describe the pharmaceutical relevance of the different
states of matter to drug delivery systems
– Describe the solid state crystallinity, solvates and
polymorphism
– Explain liquefaction of gases and its applications
Three Main
States of Matter
• Solid
• Liquid
• Gas
States of
Matter
• Gases, liquids, and the crystalline solids are the three
primary states of matter or phases
• The molecules, atoms, and ions in the solid state are held
in close proximity by intermolecular, interatomic, or ionic forces
• The atoms in the solid can oscillate only in the fixed
positions
• As the temperature of a solid substance is raised, the
atoms acquire sufficient energy to disrupt the ordered arrangement of the lattice
and pass into the liquid form
• When sufficient energy is supplied, the atoms or molecules
pass into the gaseous state
• Solids with high vapour pressures, such as iodine, and
camphor, can pass directly from the solid to gaseous state without melting at
room temperature
• This process is known as sublimation, and the reverse
process is known as deposition, that is condensation to the solid state
• Certain molecules frequently exhibit a fourth phase known
as mesophase, which lies between the liquid and crystalline state
Liquids
• The state of matter in which a substance exhibits a characteristic
readiness to flow, little or no tendency to disperse, and relatively high
incompressibility. Matter or a specific body of matter in this state. around
you. On Earth, matter is usually found in one of three states, or phases. The
three
• Liquid are close together with no regular arrangement
• Liquid vibrate, move about, and slide past each other
Solids
• A substance having a definite shape and volume; one that
is neither liquid nor gaseous
• Solid are tightly packed, usually in a regular pattern
• Solid vibrate (jiggle) but generally do not move from
place to place
Gases
• A substance possessing perfect molecular mobility and the property
of indefinite expansion, as opposed to a solid or liquid
• Gas are well separated with no regular arrangement.
• Gas vibrate and move freely at high speeds.
Physical
Changes
• Physical changes occur when objects undergo a change that
does not change their chemical nature.
A physical change involves a change in physical properties.
Physical properties can be observed without changing the type of matter.
Examples of physical properties include: texture, shape,
size, color, odor, volume, mass, weight, and density
Elements move from one phase to another
• When physical forces are present
• Examples: solid to a liquid and liquid to gas
• Physical changes happens due to:
-Increased temperature/Increased Pressure
– Decreased temperature/Decreased Pressure
Temperature
• Temperature changes materials from one state of matter to another.
Heated solids melt into liquids. Heated liquids evaporate into gases
• Cooled gases condense into liquids. Cooled liquids freeze
into solids
What is
Matter?
Matter is everything around you. On Earth, matter is usually
found in one of three states, or phases. The three main states of matter are
solid, liquid, and gas
Latent heat
of fusion
• The heat (energy) absorbed when 1g of a solid melts or the
heat liberated when it freezes is known as the latent heat of fusion
• For water the latent heat of fusion is at 0 °C is about 80
cal/g
• The heat added during the melting process does not bring
about a change in temperature until all of the solid has disappeared because
this heat is converted into the potential energy of the molecules that have
escaped from the solid into the liquid state
• The temperature at which a liquid passes into the solid
state is known as the freezing point
• It is also the melting point of a pure crystalline
compound
• The freezing point or melting point of a pure crystalline
solid is strictly defined as the temperature at which the pure liquid and solid
exists in equilibrium
• Different intermolecular forces are involved in holding
the crystalline solid together and that the addition of heat to melt the
crystal is actually the addition of energy
Vapour
pressure
• Translational energy of motion (kinetic energy) is not distributed
evenly among molecules; some of the molecules have more energy and hence higher
velocities than others at any moment
• When a liquid is placed in an evacuated container at a
constant temperature, the molecules with the highest energies break away from
the surface of the liquid and pass into the gaseous state, and some of the
molecules subsequently return to the liquid state or condense
• When the rate of condensation equals the rate of
vaporization at a definite temperature, the vapour become saturated and a dynamic
equilibrium is established
• The pressure of the saturated vapour above the liquid is
then known as the equilibrium vapour pressure
• The presence of a gas, such as air, above the liquid
decreases the rate of evaporation, but it does not affect the equilibrium pressure
of the vapour
• As the temperature of the liquid is elevated, more
molecules approach the velocity necessary for escape and pass into the gaseous
state
• As a result the vapour pressure increases with rising temperature
• A gas is known as vapour below its critical temperature
• Vapour is a substance that is a liquid or a solid at room
temperature and passes into the gaseous state when heated to a sufficiently high
temperature
• A gas is a substance that exists in the gaseous state even
at room temperature
• Menthol and ethanol are vapors at sufficiently high temperatures;
oxygen and carbon dioxide are gases
Boiling
point
• If a liquid is placed in an open container and heated
until the vapour pressure equals the atmospheric pressure, the vapour will form
bobbles that rise rapidly through the liquid and escape into gaseous state
• The temperature at which the vapour pressure of the liquid
equals the external or atmospheric pressure is known as the boiling point
• All the absorbed heat is used to change the liquid to
vapour, and the temperature does not rise until the liquid is completely
vaporized
• The heat that is absorbed when water vaporizes at the
normal boiling point (i.e., the heat of vaporization at 100 °C) is 539 cal/g
• These quantities of heat, known as latent heats of
vaporization, are taken up when the liquid vaporize and are liberated when the
vapors condense to liquids
• The boiling point may be considered the temperature at which
thermal agitation can overcome the attractive forces between the molecules of a
liquid
• Therefore, the boiling point of a compound, like the het
of vaporization and the vapour pressure at a definite temperature, provides a
rough indication of the magnitude of the attractive forces
Aerosols-inhalers
• Gases can be liquefied under high pressures in a closed chamber
as long as the chamber is maintained below the critical temperature
• When the pressure is reduced, the molecules expand and the
liquid reverts to a gas
• This reversible change of state is the basic principle
involved in the preparation of pharmaceutical aerosols
• In such products, the drug is dissolved or suspended in a propellant
• Propellant is a material that is liquid under the pressure
conditions existing inside the container but that forms a gas under normal
atmospheric conditions
• The container is so designed that, by depressing a valve,
some of the drug-propellant mixture is expelled owing to the excess pressure
inside the container
• If the drug is nonvolatile, it forms a fine spray as it
leaves the valve orifice; at the same time, the liquid propellant vaporizes off
• Chlorofluorocarbons (CFCs) and hydrofluorocarbons (HFCs)
have traditionally been utilized as propellants in these products
Liquefaction
of Gases
• Liquefaction of gases means converting of gases into
liquids
• The steps involved in this process are:
Cooled
Gas ————> Velocity of molecules decrease ———–>Liquid
• The principles of liquefaction can be studied under three
headings:
– Critical conditions
– Joule-Thomson’s effect
– Inversion temperature
Liquefaction
of Gases- Critical Conditions
• Liquefaction can be inferred as a transition from a gas to
a liquid
• It depends on temperature and pressure to which the substance
is subjected, these are critical conditions
• Critical temperature is defined as the temperature above which
the liquid can no longer exist as liquid
• Critical pressure is defined as the pressure required to
liquefy a gas at its critical temperature
• If a gas is cooled below its critical temperature, less
pressure is sufficient to liquefy it
• Critical pressure is also the highest vapour pressure that
a liquid can have
• As the temperature is increased sufficiently, a value is
reached above which it is impossible to liquefy a gas irrespective of amount of
pressure applied
• Molecules possess sufficient kinetic energy so that no
amount of pressure can bring them with in the range of attractive forces that
cause the particles to stick together
Liquefaction
of Gases- Joule-Thomson’s Effect
• When a gas is allowed to pass from a high pressure zone to
a low pressure zone, the gas expands by taking up the heat from the
surroundings, which ultimately results in cooling
• As the gas expands, the molecules fall apart from one
another
• For this to occur work has to be done to overcome the cohesive
and attractive forces
• The kinetic energy of the gas decreases, since it is
proportional to temperature
Liquefaction
of Gases- Inversion Temperature
• Gases become cooler only if they are below a certain temperature
known as inversion temperature
• Inversion temperature is defined as the temperature
characteristic of a gas below which only the gas cools when allowed to get
expanded
• At inversion temperature, there is no increase or decrease
of temperature of the surroundings
• Above inversion temperature, there is small rise and
below, there is a fall in temperature
Liquefaction
of Gases-Applications
• Liquid ammonia and sulphur dioxide are used as refrigerants
• Liquid carbon dioxide is used as in soda fountains
• Liquid air is an important source of oxygen in rockets,
jet
• propelled planes and bombs
• Compressed oxygen is used in welding
Crystalline
Solids
• The structural units of crystalline solids, such as ice,
sodium chloride, and menthol are arranged in a fixed geometric patterns or
lattices
• Most pharmaceutical solids have crystals in the size range
of 0.5-300 μm
• Crystallinity is defined as a coordination of matter
resulting from an orderly cohesive three dimensional arrangement of its
component particles in space
• Three dimensional arrangement is called crystal lattice or
space lattice
• The units that constitute the crystal structure can be
atoms, molecules and ions
• In organic compounds, the molecules are held together by
van der waals forces, Coulombic forces and hydrogen bonding
• These forces and bonding accounts for low melting points
of the crystals
• Aliphatic hydrocarbons crystallize with their chains lying
in parallel arrangement
• Ionic and atomic crystals in general are hard and brittle
and have high melting point
• Molecular crystals are soft and have low melting point
Liquid
Crystalline State- Structure
• Liquid crystals (mesophase) are intermediate between the
liquid and solid state
• The two main types of liquid crystals are termed as:
– smectic (soap like or grease like)
– nematic ( threadlike)
• In the sematic state molecules are mobile in two directions
and can rotate about one axis
• In the nematic state, the molecules again rotate only
about one axis but are mobile in three dimensions
• The sematic mesophase is of pharmaceutical significance
• This phase usually forms internary mixtures containing a
surfactant, water and a weakly amphiphilic
or nonpolar additive
• Molecules that form mesophases are –
– Organic
– Elongated and rectilinear in shape
– Rigid
– Possesses strong dipoles and easily polarizable groups
Liquid
Crystalline State- Properties and Significance
• Because of their intermediate nature, liquid crystals have
some properties of liquids and some properties of solids
• Liquid crystals are mobile and can be considered to have
flow properties of liquids
• They are birefringence where, the light passing through a
material is divided into two components with different velocities and
refractive index
• The smectic mesophase has application in the
solubilization of water insoluble materials
• Liquid crystalline phases are present in emulsions and responsible
for physical stability owing to their highly viscous nature
• The lipoidal forms of liquid crystalline state is found in
nerves, brain tissue and blood vessels
• Three components of bile (cholesterol, bile acid salt and
water) can form a smectic mesophase
• The principle of liquid crystal formation can be applied
to the solubilisation and dissolution of cholesterol
• Liquid crystals have structures that are similar to those
in cell membranes
Polymorphism
• Polymorphism is the ability of a compound to crystalize as
more than one distinct crystalline species with different internal lattices
• Polymorphism is exhibited by 63% of barbiturates, 76% of steroids
and 40% of sulphonamides
• If an element crystallizes in more than one distinct
crystalline species, this phenomenon is called as allotropy
• The polymorph with highest melting point is stable form
• The other polymorphic forms are categorised as unstable
and metastable
• Polymorphs are structurally not different, but exhibit differences
in their physicochemical and biological properties
• The properties are melting point, solubility, dissolution
and bioabsorption
• Polymorphs are prepared by manipulation of conditions of crystallization
such as solvent, temperature and rate of cooling
• Metastable polymorphs are important for the formulation
but these slowly convert into a stable form during storage
Polymorphism-
Applications
• Enhanced solubility
• Improved dissolution
• Enhanced absorption
• Manufacture of dosage forms
Relative
humidity
• Measures the amount of water vapor in the atmosphere (humidity)
relative to the maximum amount of water vapor in the atmosphere could hold at
the same temperature
• Affects the heating and cooling of air
• Warm air can hold more water vapor and the saturation
point of the air is higher than for cold air
• Water vapor has the strongest impact as a greenhouse gas
• Specific humidity refers to the actual amount of water
vapor in the air
• Taking RH measurements helps us understand how quickly water
will move from the surface of the Earth to the atmosphere and then back to
Earth
• RH measurements are important in classifying an area as
arid (dry), or humid (moist)
• RH influences when clouds will form and when precipitation
will fall
• The amount of water in the atmosphere is one of the determining
factors in the weather and climate in an area
• RH affects the heating and cooling of the air
• Because of its high heat capacity, water vapor can greatly
change the rate that air masses change temperature.
Eutectic
Mixtures
• A simple eutectic mixture consists of two components which
are completely miscible in liquid state but to a limited extend in solid state.
These are prepared by rapid solidification of fused melt of two components.
When a mixture of poor water soluble drug and water soluble carrier is
dissolved in aqueous medium, the carrier is dissolved rapidly, releasing very
fine crystal of drug.
Solid
solutions
• In a solid solution, the two components crystallize
together in a homogeneous one phase system. The particle size of the drug in
the solid solution is reduced to its molecular size responsible for increase in
dissolution rate. On the extend of miscibility of two components, solid
solution is classified as continuous and discontinuous. In continuous solid
solution, the two components are miscible in the solid state in all proportions.
In discontinuous solid solutions, the solubility of each of the components in
the other component is limited
• Solid dispersion and eutectic formation affects the
solubility and /or the dissolution rate. Intrinsic or saturation solubility of drug
and its dissolution are two different processes. Although dissolution behavior
of any dosage form depends a lot on the former parameter, dissolution is a
kinetic phenomenon whereas saturation solubility is a thermodynamic phenomenon.
By saying kinetic phenomenon, it means that dissolution behavior depends on how
a drug molecule after getting solubilized bypasses the diffusion layer of
saturated drug solution into the bulk media and remain solubilized there until
it gets absorbed
Amorphous
Solids
• Amorphous solids may be considered as supercooled liquids in
which the molecules are arranged in a random manner as in the liquid state
• Substances such as glass, pitch, and many synthetic
plastics are amorphous solids
• They differ from crystalline solids in that they tend to
flow when subjected to sufficient pressure over a period of time and they do
not have definite melting points
• Amorphous substances, as well as cubic crystals, are
usually isotropic, that is, they exhibit similar properties in all directions
• It is not always possible to determine by casual
observation whether a substance is crystalline or amorphous
• Beeswax and paraffin, although they appear to be
amorphous, assume crystalline arrangements when heated and then allowed to cool
slowly
• Whether a drug is amorphous or crystalline has been shown
to affect its therapeutic activity
• The crystalline form of
the antibiotic novobiocin acid is poorly water absorbed and has no
activity, whereas the amorphous form is readily absorbed and therapeutically
active
• This is due to the differences in the rate of dissolution
and once dissolved, the molecules exhibit no memory of their origin
Summary
• Plane polarised
light- When light is allowed to pass through a polarizing prism (Nicol
prism), light vibrations in only one plane are transmitted, and such a light
beam is known as plane polarized light
• Optical activity –
It is the ability of certain substances to rotate the plane polarized light
• Optically active
substances – These are the substances which can rotate the plane polarized
light either to right- side or to left- side
• Dextrorotatory
substances rotate the plane polarised light towards the right, has an α, that
is defined as positive
• Levorotatory
substances rotate the plane polarised light towards left, has an α, that is
defined as negative
• Specific rotation –
The specific rotation, at a specified temperature t and
wavelength λ is given by the equation
• A polarimeter is used to measure optical rotation
• Dielectric constant
– It is a physicochemical property of a solvent relating to the amount of
energy required to separate two oppositely charged regions in the solvent as
compared to the energy required to separate the same in vacuum
• Dielectric constant can be given as:
Cx
ε = ——-
C0
• Dielectric constant is dimensionless
• The heat (energy) absorbed when 1g of a solid melts or the
heat liberated when it freezes is known as the latent heat of fusion
• The temperature at which a liquid passes into the solid
state is known as the freezing point
• When the rate of condensation equals the rate of vaporization
at a definite temperature, the vapour become saturated and a dynamic
equilibrium is established
• The pressure of the saturated vapour above the liquid is
then known as the equilibrium vapour pressure
• Vapour is a substance that is a liquid or a solid at room
temperature and passes into the gaseous state when heated to a sufficiently high
temperature
• The temperature at which the vapour pressure of the liquid
equals the external or atmospheric pressure is known as the boiling point
• Latent heats of vaporization, are taken up when the liquid
vaporize and are liberated when the vapors condense to liquids
• When the pressure is reduced, the molecules expand and the
liquid reverts to a gas
• This reversible change of state is the basic principle
involved in the preparation of pharmaceutical aerosols
• Liquefaction of
gases- means converting of gases into liquids
• Liquefaction –
It is transition from a gas to a liquid
• Critical
temperature – It is defined as the temperature above which the liquid can
no longer exist as liquid
• Critical pressure –
It is defined as the pressure required to liquefy a gas at its critical
temperature
• Inversion
temperature- It is defined as the temperature characteristic of a gas below
which only the gas cools when allowed to get expanded
• Crystallinity –
It is defined as a coordination of matter resulting from an orderly cohesive
three dimensional arrangement of its component particles in space
• Polymorphism –
It is the ability of a compound to crystalize as more than one distinct
crystalline species with different internal lattices
• Measures the amount of water vapor in the atmosphere
(humidity) relative to the maximum amount of water vapor in the atmosphere
could hold at the same temperature
• Specific humidity refers to the actual amount of water
vapor in the air
• Because of its high heat capacity, water vapor can greatly
change the rate that air masses change temperature
• A simple eutectic mixture consists of two components which
are completely miscible in liquid state but to a limited extend in solid state
• These are prepared by rapid solidification of fused melt
of two components
• In a solid solution, the two components crystallize
together in a homogeneous one phase system
• The particle size of the drug in the solid solution is
reduced to its molecular size responsible for increase in dissolution rate
• Amorphous solids may be considered as supercooled liquids
in which the molecules are arranged in a random manner as in the liquid state
• The crystalline form of
the antibiotic novobiocin acid is poorly water absorbed and has no
activity, whereas the amorphous form is readily absorbed and therapeutically
active
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