States of Matter

Presented By
Dinesh Kumar Sharma
 States of Matter
 Binding Forces Between Molecules
 Solids and the Crystalline State
 Phase Equilibria and the Phase Rule
 Objectives of the lecture
After completion of this chapter, the students should be able to:
 Describe the solid state , crystallinity, solvates and polymorphism
Understand phase equilibria and phase transitions between the three
main states of matter
Understand the phase rule and its application to different systems
containing multiple components.
 Comparison of Gases, Liquids and Solids
 Gases are compressible fluids. Their molecules are widely separated.
 Liquids are relatively incompressible fluids. Their molecules are more tightly packed.
 Solids are nearly incompressible and rigid. Their molecules or ions are in close contact
and do not move.

In order for molecules to exist in aggregates in gases, liquids

and solids Intermolecular forces must exist
 Repulsive and Attractive Forces
 As two atoms or molecules are brought closer
together, the opposite charges and binding
forces in the two molecules are closer
together than the similar charges and forces,
causing the molecules to attract one another.

 The negatively charged electron clouds of

molecules largely govern the balance
(equilibrium) forces between the two
molecules
 Ideal Gas Equation
1
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)

P1V1 P2V2 R is the gas

T1
= PV = nRT
T2 constant
 Gaseous state
 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 22.414

L.

PV = nRT
PV = (1 atm)(22.414L)
R=
nT (1 mol)(273.15 K)

R = 0.082057 L • atm / (mol • K)

 Liquefaction of Gases
 The critical temperature (Tc) is the temperature above which the gas cannot be
made to liquefy, OR is the temperature above which the liquid cannot longer exist

 The critical pressure (Pc) is the minimum pressure required to liquefy a gas at its
critical temperature.

 critical temperature (Tc) of water is 374°C, or 647 K, and its critical pressure is 218
atm,
 SOLIDS & CRYSTALLINE STATE
Pharmaceutical Drugs: more than 80% are solid formulations
 Solids and the crystalline state
 A crystalline solid possesses rigid and long-range order.

 In a crystalline solid, atoms, molecules or ions occupy specific

(predictable) positions.

 An amorphous solid does not possess a well-defined arrangement

and long-range molecular order.
 Classification of Solids

Crystalline Amorphous

 Amorphous
A unit cell is the basic repeating structural unit of a crystalline solid.

lattice
point
At lattice points:
• Atoms
• Molecules
• Ions

Unit Cell Unit cells in 3 dimensions

The crystal lattice of sodium chloride NaCl

Na Cl
 Crystal forms
The various crystal forms are divide to basic 7 unit according to its symmetry
NaCl urea iodoform

iodine

Be3Al2(SiO3)6
sucrose Boric acid
 Types of Crystals
Ionic Crystals
• Lattice points occupied by cations and anions
• Held together by electrostatic attraction
• Hard, brittle, high melting point
• Poor conductor of heat and electricity

CsCl ZnS CaF2

Covalent Crystals
• Lattice points occupied by atoms
• Held together by covalent bonds
• Hard, high melting point
• Poor conductor of heat and electricity

carbon
atoms

diamond
graphite
Metallic Crystals
• Lattice points occupied by metal atoms
• Held together by metallic bonds
• Soft to hard, low to high melting point
• Good conductors of heat and electricity

nucleus &
inner shell e-

mobile “sea”
of e-

Cross Section of a Metallic Crystal

 Polymorphism
 Some elemental substance such as C
and S ,may exist in more than one
crystalline form and are said to be
allotropic, which is a special case of
polymorphism

 Polymorphism is the ability of a

substance to exist in more than one
crystal structure
Polymorphism is the ability of a substance to exist in more than one
crystal structure

 Polymorphs: when two crystals have the same chemical composition

but different internal structure (molecular packing –molecular
conformation or / and inter or intra molecular
interactions)modifications or polymorphs or forms

Pseudo polymorphs : different crystal forms have molecules of the

same given substances and also contain molecules of solvent
incorporated into a unique structure (solvates or hydrates (water))
 The most common example of polymorphism

carbon
atoms

High T and p
diamond graphite

Diamond is metastable and converts very slowly to graphite

 Solid State : Polymorphs

 Mono-component systems: Polymorphs

 Multi-component systems
 Cocrystal
 The simplest definition of a cocrystal is a crystalline structure made up
of two or more components in a definite stoichiometric ratio, where
each component is defined as either an atom, ion, or molecule.
 Principle of polymorphism
 When the change from one form to another is reversible, it is said to
be enantiotropic.

 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.
 Solvates
 Pharmaceutical synthesis include purification and crystallization,
residual solvent can be trapped in the lattice.
 This result in the formation of cocrystal or solvate.

 The presence of residual solvent may affect dramatically the

crystalline structure of the solid depending on the type of inter.
molecular forces that the solvent may have with crystalline solid
 Polymorphism
Melting point Photochemical reactivity
Vapor pressure Thermal stability
Hardness Filtration and drying characteristics
Optical, electrical magnetic Dissolution rate
properties Bioavailability
Color Physical and chemical stability
IR spectra
NMR spectra

Solubility and melting point are very important in pharmaceutical

processes including dissolution and formulation.
 Amorphous Solid
 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.

AMORPHOUS SOLIDS
Solids that don’t have a definite geometrical shape are known as Amorphous Solids.
1. In these solids particles are randomly arranged in three dimension.
2. They don’t have sharp melting points.
3. Amorphous solids are formed due to sudden cooling of liquid.
4. Amorphous solids melt over a wide range of temperature
 Amorphous or crystalline & therapeutic
activity
 The crystalline from of the antibiotic novobiocin acid is poorly
absorbed and has no activity, where the amorphous form is readily
absorbed and therapeutically active, due to different dissolution rate.
 Crystallization
General crystallization conditions
Solvents –different polarities
Concentration of the solutions (super saturated, saturated, diluted)
Cooling speed (quenching, slow)
Temperature (room or lower than room temperature)
 Polymorphism and Industry/ Pharmaceutical

API Final Form

Crystallization Granulation

Filtration Drying

Drying Compaction

Milling Tableting

Bulk API Drug Product

Stability
THANK YOU