STATES OF MATTER
(Dr) Kahnu Charan Panigrahi
Asst. Professor, Research Scholar,
Roland Institute of Pharmaceutical Sciences,
(Affiliated to BPUT)
Web of Science Researcher ID: AAK-3095-2020
Gases are compressible fluids. Their molecules are widely separated.
Liquids are relatively incompressible fluids. Their molecules are more tightly
Solids are nearly incompressible and rigid. Their molecules or ions are in close
contact and do not move.
Comparison of Gases, Liquids and Solids
A crystalline solid possesses rigid and long-range specific order.
In a crystalline solid, atoms, molecules or ions occupy (predictable)
An amorphous solid does not possess a well-defined arrangement
and long-range molecular order.
Solids and the crystalline state
According to the nature of bond classified to fallowing group:
• Ionic Crystals
• Covalent Crystals
• Metallic Crystals
Types of Crystals
No. of crystal system = 7
No. of Space lattice = 14
No. of Geometric structure = 230
POLYMORPHISIM, PSEUDOPOLYMORPHISIM AND AMORPHISM
INTERNAL STRUCTURE OF
ORGANIC SOLVATE HYDRATES
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• Polymorphism is the ability of a substance to exist in more than one crystal
• When the change from one form to another is reversible, it is said to be
• When the transition takes place in one direction only—for example, from a
metastable to a stable form—the change is said to be monotropic.
• Element exist in two or more distinct crystalline species called as allotropy.
• Form having high melting point and low solubility are stable form, while
form having low melting point and high solubility called metastable form
Applications of Polymorphism
SOLUBILITY: Riboflavin form I < form II < form III
DISSOLUTION: Methylprednisolone form I < form II
Melting point of Coca butter:
Theobroma oil can exist in 4 different polymorphic forms of which only one is
1. Unstable gamma form melting at 18°C
2. Alpha form melting at 22°C
3. Beta prime form melting at 28°C
4. Stable beta form melting at 34.5°C
If the oil is heated to a point where it is completely liquified (about 35 C), the
crystals of the stable polymorph are destroyed & the mass does not crystallize
until it is cooled to 15 C.
The crystals that form are unstable & the suppositories melt at 24 C.
Theobroma suppositories must be prepared below 33 C.
• Pseudomorphs are defined as those solid which form inclusion of small
amount of solvent.
• In case of stoichimetric type of adduct, the solvent molecules are
incorporated in the crystal lattice which are called as solvates and the
solvent called as solvent of crystallisation.
• When the solvent associated is water then solvate are called as hydrate.
• Generally anhydrous form has grater water solubility than the hydrates
• organic solvates have better aqueous solubility than anhydrous form.
• The anhydrous form of ampicillin have higher aqueous solubility then
• Chloroform solvate of griseofluvin have more aqueous solubility than non-
An amorphous solid does not possess a well-defined arrangement and long-
range molecular order.
Amorphous substances, as well as cubic crystal, are isotropic, that is, they
exhibit similar properties in all direction.
In these solids particles are randomly arranged in three dimension.
They don’t have sharp melting points.
Amorphous solids are also known as super cooled liquid.
Amorphous solids melt over a wide range of temperature
• Increasing order of melting point
AMORPHOUS < METASTBLE < STABLE
• Increasing order of solubility
STABLE < METASTBLE <AMORPHOUS
• The crystalline from of novobiocin acid is poorly absorbed,
where as the amorphous form is readily absorbed and
Differential scanning calorimetry
• PRINCIPLE: It is a technique in which the difference in heat
required to increase temperature of the sample & reference
material is measured as a function of temp. or time.
• Endothermic reaction: if sample absorbs some amount of heat
during phase transition then reaction is said to be
endothermic. Downward peak result
• E.g. Melting, boiling, sublimation, vaporization, de-solvation.
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• Exothermic reaction: if sample released some amount of heat during
phase transition, then reaction is said to be exothermic. Upward peak
• E.g crystallization, degradation, polymerization
• Glass Transition temp(Tg): Temp at which an amorphous polymer or an
amorphous part of crystalline polymer goes from hard , brittle state to
soft or rubbery state.
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Application of DSC
• During pre-formulation, it is important to identify the polymorph that
• A sharp melting endotherm indicates the relative purity where as broad
asymmetric curve suggest impurity.
• DSC with the support of x-ray diffraction & infrared spectroscopy are
used as screening technique for the compatibility testing of drug with
• The disappearance of the DSC peak of the drug is the proof of
complexation in solid state.
X-RAY POWDER DIFFRACTION
• X-RAY powder diffractometry is used to characterize spray dried,
crystalline material & the binary mixtures.
• x-ray are diffracted & order of this diffraction is measured in form of
graph between spectra intensity vs 2ɵ (0-40)
• Diffraction occurs as a result of the interaction of radiation with electron
• Because x-rays have wavelengths of about the same magnitude as the
distance between the atoms or molecules of crystal.
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Application of X-ray diffraction
• Structure of Crystals
• Polymer Characterization
• Identification Of Impurity
• identify the solvated and anhydrous forms of a compound
• XRD is widely used to determine the degree of crystallinity of
When X ray is diffracted by the atom a relationship between
wavelength, angle of incidence light and distance between
successive atomic plane was established as:
nƛ = 2d sin ɵ
Where n = 1,2,3 … order of reflection
This equation is applied to calculate distance between the plane.
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XRD patterns of (a) crystalline and (b) amorphous sucrose
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Degree of crystallinity
• Liquids are denser than gases and occupy a definitevolume and density due to the
presence of van der Waalsforces unlike gases.
• Liquid have no definite shape like gases
• Liquids have translational motion i.e. liquids move as a whole
• If we allow gas to expand rapidly (inside a vacuum flask) so that no heat enters system,
such expansion is known as adiabatic expansion.
• As a result of that temperature of gas reduces. This cooling effect is known as Joule-
• Inversion temperature is the temperature below which gas cool when expand. (H= -80C
and He =-240C)
• When the rate of condensation equals the rate of vaporization at a definite temperature,
the vapour becomes saturated and a dynamic equilibrium is established.
• The pressure of the saturated vapour above the liquid is then known as the equilibrium
Vapor pressure of liquids
• Any point on one of the curve
represents a condition in which the
liquid and the vapor exist together
• If the temperature of any of the
liquids is increased while the pressure
is held constant, or if the pressure is
decreased while the temperature is
held constant, all the liquid will pass
into the vapour state.
• The area covering right side of curve
represent vapour phase while on left
side represent liquid phase.
Vapor pressure of liquids
Clausius–Clapeyron equation expresses the relationship
between the vapor pressure and the absolute temperature of a liquid:
𝑷𝟐 ∆𝑯𝒗 𝑻𝟐−𝑻𝟏
𝑷𝟏 2.303 𝑹𝑻𝟏𝑻𝟐
P1 and P2: vapor pressures at absolute temperatures T1 and T2.
ΔHv: the molar heat of vaporization (the heat absorbed by 1 moleof liquid
when it passes into the vapor state). For water it is 40.67MJ/kmol
The temperature at which the vapor pressure of the liquid equals the
external or atmospheric pressure isknown as the boiling point.
The absorbed heat used to change the liquid to vapor (at constant
temperature i.e., boiling point) is called the latent heats of vaporization.
For water it is 40.67MJ/kmol
• The temperature at which the vapor pressure of the liquid equals an
atmospheric pressure of 1 atm is called normal boilingpoint
• At higher elevations, the atmospheric pressure decreases and the boiling
point is lowered.
• At a pressure of 700 mm Hg, water boils at 97.7°C; at 17.5 mm Hg, it boils at
• The change in boiling point with pressure can be computed by using the
• Polar molecules (e.g water) exhibit high boiling points and high heats of
vaporization because they are associated through hydrogen bonds.
• Alcohols boil at a much higher temperature than saturated hydrocarbons
through hydrogen bonding.
• The boiling points of carboxylic acids are higher than that of alcohols
because the acids form dimers through hydrogen bonding.
Critical temperature (Tc) is the temperature above which the gas cannot be made to
liquefy, OR is the temperature above which the liquid can no longer exist
The critical pressure (Pc) is the minimum pressure required to liquefy a gas at its
Critical temperature (Tc) of water is 374°C, or 647 K, and its critical pressure (Pc) is
218 atm or 22.08 pa.
• Critical temperature (Tc) of Carbon dioxide is 31.1°C, and its critical pressure (Pc) is
Liquefaction of Gases
• When a compound is subjected to a pressure and a temperature
higher than its critical point, the fluid is said to be " supercritical " .
• In the supercritical region, the fluid exhibits particular proporties and
has an intermediate behaviour between that of a liquid and a gas.
• In particular, supercritical fluids (SCFs) possess liquid-like densities,
gas-like viscosities and diffusivities intermediate to that of a liquid
and a gas. And hence termed as mesophase.
• The fluid is said "supercritical" when it is heated above its critical
temperature and compressed above its critical pressure.
• Carbon dioxide (CO2) is the most widely used supercritical
fluid. This is because CO2 is chemically inert, non-toxic, non-
flammable and the critical point of CO2 is easily accessible. (critical
temperature 31°C and critical pressure 74 bar).
• Due to its interesting properties Supercritical CO2 can be
described as a ‘green solvent’.
• All supercritical fluids are completely miscible with each other
• Application: food extraction, volatile oil extraction,
chromatography, Elimination of toxic substance, Crystallisation of
• Liquid crystals (LCs) are a state of matter which has properties
between those of conventional liquids and those of solid crystals. For
instance, a liquid crystal may flow like a liquid, but its molecules may
be oriented in a crystal-like way hence posses refractive index.
• In a nematic phase ("thread-like") the molecules are aligned in the same
direction but are free to drift around randomly, very much as in an
• Owing to their polarity, the alignment of the rod-like molecules can be
controlled by applying an electric field.
• In smectic ("soap-like") phases the molecules are arranged in layers, with
the long molecular axes approximately perpendicular to the laminar
• The only long-range order extends along this axis, with the result that
individual layers can slip over each other (hence the "soap-like" nature) in
a manner similar to that observed in graphite.
• Cholesteric liquid crystal is a combination of nematic and smectic type.
Ideal Gas Equation
Boyle’s law: P V (at constant n and T)
Charles’ law: V T (at constant n and P)
Avogadro’s law: V n (at constant P and T)
PV = nRT
R is the gas constant
Combined Gas Equation
GASEOUS STATE LAW
The conditions 0 0C and 1 atm are called standard temperature
and pressure (STP).
Experiments show that at STP, 1 mole of an ideal gas occupies
PV = nRT
R = PV =
(1 mol)(273.15 K)
R =0.082057 L • atm / (mol • K)
What is the volume (in liters) occupied by 49.8 g of HCl at STP?
PV = nRT
T = 0 0C = 273.15 K
P = 1 atm
n = 49.8 g x
1 mol HCl
36.45 g HCl
= 1.37 mol
1.37 mol x 0.0821 L•atm
x 273.15 K
V = 30.7 L
1 atm ≈760.001 mm-Hg
Phase Equilibria & The Phase Rule
Gibbs phase rule stated as:
A gaseous mixture of CO2 and N2:F = 2 - 1 + 2 = 3
Three variables: pressure, temperature and composition. This is
a trivariant system.
A phase is defined as any homogeneous and physically distinct part of a system
which is separated from other parts of the system by interfaces.
A part of a system is homogeneous if it has identical physical properties and
chemical composition throughout the part.
Liquid water, pieces of ice and water vapour are present together. The number
of phases is 3 as each form is a separate phase.
Calcium carbonate undergoes thermal decomposition. The chemical reaction
CaCO3(s) = CaO (s) + CO2 (g)
Number of phases = 2 : This system consists of 2 solid phases, CaCO3 and CaO
and one gaseous phase, that of CO2
The number of components of a system at equilibrium is the smallest
number of independently varying chemical constituents using which the
composition of each and every phase in the system can be expressed.
A mixture of ethanol and water is an example of a two component system.
We need both ethanol and water to express its composition.
Degrees of freedom
The degrees of freedom is the least number of intensive property which
must be fixed in order to define the system completely.
The Critical Solution Temperature: CST
Is the maximum temperature at which the
two conjugate solution merges into one
layer in all proportion. (or upper
In the case of the phenol-water system,
this is 66.8oC (point h) at 34% phenol
All combinations of phenol and water >
CST are completely miscible and yield 1-
phase liquid systems.
Application: Purity of phenol
TRIETHANOLMINE – WATER
SYSTEM, CST: 18.5 C AT 50%
NICOTINE – WATER SYSTEM AT
32% FOR UPPER AND 22% FOR
A eutectic mixture is defined as a mixture of two or more components
which usually do not interact to form a new chemical compound but, which
at certain ratios, inhibit the crystallization process of one another resulting
in a system having a lower melting point than either of the components
EMLA® (lidocaine 2.5% and prilocaine 2.5%) Cream
EMLA Cream (lidocaine 2.5% and prilocaine 2.5%) is an emulsion in which
the oil phase is a eutectic mixture of lidocaine and prilocaine in a ratio of
1:1 by weight. This eutectic mixture has a melting point below room
temperature at 18 C and therefore both local anesthetics exist as a liquid
oil rather than as crystals
Eutectic mixture : Pharmaceutical Application
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