States of matter & Phase Equilibria

1. Khalid T Maaroof
MSc. Pharmaceutical sciences
School of pharmacy – Pharmaceutics department
1
Online access: bit.ly/physicalpharmacy
Statesofmatter
Physical Pharmacy
10/31/2015

2. This
lecture
Bonds
Intermolecular
Van der vals and
dipole bonds
Ionic bonds & Ion
dipole bonds
Hydrogen bondsIntramolecular
States of matter
Solids
Crystalline
solids
Polymorphs
Solvates
Melting point
and heat of
fusion
Amorphous
solidsLiquids
Gases
Ideal gas law
Liquefaction of
gases
Aerosols
Other states of
interest
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3. Bonding forces
Intermolecular
forces
Intramolecular
forces
Repulsive forces
Attractive forces
In order for molecules to exist in aggregates in gases, liquids, and solids,
intermolecular forces must exist.
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4. 10/31/2015 4

5. Intermolecularforces
Van derWaals
Forces
H- Bonding
Ion-Ion
interactions
Ion-dipole
interactions
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6. Dipole
• A polar molecule that has two poles.
Van derWaals Forces
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7. Van der Waals Forces
• nonionic interactions between molecules, yet
they involve charge–charge interactions
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8. Hydrogen bond or hydrogen bridge
• Because of the small size of a hydrogen atom and its
large field, it can move in close to the electronegative
atom (fluorine, oxygen, or nitrogen) and form an
electrostatic connection.
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9. Ion–Ion Interactions
Strong forces between counter ions.
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10. Ion-dipole and ion-induced dipole forces
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11. Questions !
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12. States of matter
• Gases, liquids, and crystalline solids are the
three primary states of matter.
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13. Solids
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14. Melting point of crystalline solids
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 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.
 Normal freezing or melting point (at 1
atm)
 heat of fusion: the heat required to increase the
interatomic or intermolecular distances in crystals,
thus allowing melting.
 How intermolecular forces affect heat
of fusion???
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15. Crystalline solids
• The units that constitute the crystal structure can be atoms,
molecules, or ions. The sodium chloride crystal, consists of a
cubic lattice of sodium ions interpenetrated by a lattice of
chloride ions, the binding force of the crystal being the
electrostatic attraction of the oppositely charged ions.
• In diamond and graphite, the lattice units
consist of atoms held together by covalent
bonds.
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16. • In organic compounds, the molecules are held together by
van der Waals forces and hydrogen bonding, which account
for the weak binding and for the low melting points of these
crystals.
• ionic and atomic crystals in general are hard and brittle and
have high melting points
• molecular crystals are soft and have relatively low melting
points.
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17. 17
 Molecular weight, type of intermolecular bonds and
molecular configuration, all can affect melting and
freezing point of compounds.
 In the picture below even number chains have higher
melting points compared to odd number chains (No,
of carbons) Why???
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18. Polymorphism
• When a substance exists in more than one crystalline form, the
different form are designated as polymorphs and the phenomenon
as polymorphism.
• Polymorphs have different stabilities and may spontaneously
convert from the metastable form at a temperature to the stable
form.
• carbon: diamond in a cubic
(tetrahedral lattice arrangement )
• Graphite in sheet of a hexagonal
lattice
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19. 19
 Depending upon their relative stability, one of the
several polymorphic form will be physically more
stable than others.
 Stable polymorph represents the lowest energy
state, has highest melting point and least aqueous
solubility.
 Metastable form represent the higher energy state,
have lower melting point and high aqueous solubility
.
 Metastable form converts to the stable form due to
their higher energy state.
 Metastable form shows better bioavailability and
therefore preferred in formulations.
 Only 10% of the pharmaceuticals are present in their
metastable form.10/31/2015

20. 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.
 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 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
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21. The Liquid state
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22. Boiling
If a liquid is placed in an open
container and heated until the
vapor pressure equals the
atmospheric pressure, the vapor
will form bubbles that rise
rapidly through the liquid and
escape into the gaseous state.
 The temperature at which the
vapor pressure of the liquid
equals the external or
atmospheric pressure is
known as the boiling point.
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23.  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
heat of vaporization and the vapor pressure at a
definite temperature, provides a rough indication of
the magnitude of the attractive forces.
 The boiling points of normal hydrocarbons, simple
alcohols, and carboxylic acids increase with
molecular weight. WHY??
 Polar molecules usually have higher boiling point
than nonpolar. WHY??
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24. Heat of Vaporization & critical temperature
• Clausius–Clapeyron Equation:
 where p1 and p2 are the vapor pressures at absolute
temperatures T1 and T2, and ∆Hv is the molar heat of
vaporization, that is, the heat absorbed by 1 mole of
liquid when it passes into the vapor state.
 Heats of vaporization vary somewhat with temperature.
For example, the heat of vaporization of water is 539
cal/g at 100◦C; it is 478 cal/g at 180◦C,
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25. Gases
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26. • Ideal Gases
• Real Gases
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27. Ideal gas law
Molar gas constant:
= 0.08205 liter atm/mole K
= 8.314 × 106 erg/mole K
= 1.987 cal/mole deg
For calculations related to this slide refer to the
book
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29. Molecular weight
 Molecular weight can be determined using ideal gas
law:
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30. The van derWaals Equation for Real Gases
internal pressure per mole
resulting from the
intermolecular forces of
attraction between
the molecules
incompressibility of the
molecules, that is, the
excluded volume,
which is about four
times the molecular
volume
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31.  When the volume of a gas is large, the molecules
are well dispersed. Under these conditions, a/V2 and
b become insignificant with respect to P and V,
respectively. Under these conditions, the van der
Waals equation for 1 mole of gas reduces to the
ideal gas equation, PV = RT, and at low pressures,
real gases behave in an ideal manner.
Refer to the book example 2-5 chapter 2
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32. Liquefaction of Gases
 When a gas is cooled, it loses some of its kinetic energy
in the form of heat, and the velocity of the molecules
decreases.
 critical temperature: Above which it is impossible to
liquefy a gas irrespective of the pressure applied
 critical pressure: The pressure required to liquefy a gas
at its critical temperature which is also the highest vapor
pressure that the liquid can have.
 The further a gas is cooled below its critical temperature,
the less pressure is required to liquefy it.
 The critical temperature of water is 374◦C, or 647 K. and
its critical pressure is 218 atm,
 At critical temperature ∆Hv of water = ???32 10/31/2015

33. Aerosols
 Advantages of aerosols. [refer to the book]
 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.
 Propellant: material that is liquid under the pressure
conditions existing inside the container but that forms a gas
under normal atmospheric conditions.
 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 and hydrofluorocarbons
 nitrogen and carbon dioxide.
 Metered dose inhalation products???
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34. Other Phases of matter
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 The liquid crystalline state: Liquid
Solid
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35. 35
 Supercritical fluid state: Liquid Gas
Critical temperature and pressure?
High density close to liquids, and low viscosity close to
gases
 A gas that may have little to no ability to dissolve a
compound under ambient conditions can completely
dissolve the compound under high pressure in the
supercritical range.
 They are used for: extraction, crystallization, and
preparation of formulations
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36. Advantages of supercritical fluids when used as solvents
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 the potential for low temperature extractions
 selectivity of the extracted compounds
 lower energy requirement and lower viscosity than
solvents.
 reduced toxicity and need for hazardous solvents that
require expensive disposal
 An example is supercritical CO2, and the process of
decaffeination of coffee.
Refer to the book p37
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37. Questions !
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