States of Matter

Download as pptx, pdf, or txt
Download as pptx, pdf, or txt
You are on page 1of 100

Physical Pharmacy

Ninevah University / College of Pharmacy


2nd year
2024 – 2025

Assist. Prof.
Dr Hasan Aldewachi
1st course syllabus
No. Lecture title Hours

1. States of matter, binding forces between molecules, gases, liquids, 10


solid and crystalline matters; phase equilibria and phase rule;
thermal analysis

2. Thermodynamics, first law, thermochemistry, second law, third law, 8


free energy function and applications

3. Solutions of non-electrolytes, properties, ideal and real colligative 7


properties, molecular weight determination

4. Solution of electrolytes, properties, Arrhenius theory of dissociation, 5


theory of strong electrolytes, ionic strength, Debye-Huchle theory,
coefficients for expressing colligative properties

5. Ionic equilibria, modern theories of acids, bases and salts, acid-base 8


equilibria, calculation of pH, acidity constants, the effect of ionic
strength and free energy

6. Buffered and isotonic solutions: Buffer equation; buffer 7


capacity; methods of adjusting tonicity and pH; buffer and
biological system
Reference
What is Physical Pharmacy
Learning Goals

 Explain how attractive and repulsive


forces govern the interaction between
atoms.
 Describe the effect of potential well depth
on atomic interactions.
 Contrast the potential well of a bonded
pair of atoms with unbonded pairs.
 Describe bonds as dynamic and bond
lengths as average distances.
the potential energy-interatomic spacing
curve

In general, as the atoms move away from each other (increasing


interatomic spacing), the potential energy of the system increases,
and as they come closer (decreasing interatomic spacing), the
potential energy of the system also increase
Here are some examples of a polar covalent bond with the
electronegativity difference between the two bonding atoms

Electronega
Compound Molecular tivity
Bond
Name formula difference [1
]

Water H2O O-H 1.4

Hydrogen
HF H-F 1.9
fluoride

Hydrogen
HCl H-Cl 0.9
chloride

Hydrogen
HBr H-Br 0.7
bromide

Ammonia NH3 N-H 0.9

Sulfur dioxide SO2 S=O 1

Hydrogen
H2S H-S 0.4
sulfide

Methanol CH3OH O-H 1.4


Intermolecular Forces

 https://www.youtube.com/watch?v=9YwdeEDrfPI

What Are Intermolecular Forces | Properties of Matt


er | Chemistry |
FuseSchool - YouTube
Dipole-Dipole Interactions

The more polar the molecule, the higher is its


boiling point.
Relation of van der Waals forces with
distance
 In all three types of van derWaals forces, the potential energy of
attraction varies inversely with the distance of separation, r, raised to
the sixth power, r6.
 The potential energy of repulsion changes more rapidly with distance,
At a certain equilibrium distance, about (3–4) x 10−10 m (3–4 A° ), the
repulsive and attractive forces are equal. At this position, the
potential energy of the two molecules is a minimum and the system
is most stable
 An important dipole–dipole force is the interaction between pi-
electron orbitals in systems.
 For example, aromatic– aromatic interactions can occur when the
double-bonded pi orbitals from the two rings overlap).
 Aromatic rings are dipolar in nature, having a partial negative charge
in the pi-orbital electron cloud above and below the ring and partial
positive charges residing at the equatorial hydrogens
 These interactions are dipole–dipole in nature and they are
introduced to highlight their importance
Factors Affecting London Forces
• The shape of the molecule affects the
strength of dispersion forces: long, skinny
molecules (like n-pentane tend to have
stronger dispersion forces than short, fat
ones (like neopentane).
• This is due to the increased surface area in
n-pentane.

Intermolecular
Forces
Factors Affecting London Forces

• The strength of dispersion forces tends to increase with


increased molecular weight.
• Larger atoms have larger electron clouds, which are easier to
polarize.
Intermolecular
Forces
PRACTICE EXERCISE
Of Br2, Ne, HCl, HBr, and N2, which is likely to have (a) the
largest intermolecular dispersion forces, (b) the largest
dipole-dipole attractive forces?

Answers: (a) Br2 (largest molecular weight), (b) HCl (largest polarity)

Intermolecular
Forces
How Do We Explain This?

• The nonpolar series (SnH4


to CH4) follow the expected
trend.
• The polar series follows the
trend from H2Te through
H2S, but water is quite an
anomaly.

Intermolecular
Forces
Hydrogen bonding
 The interaction between a molecule containing a hydrogen atom and a
strongly electronegative atom such as fluorine, oxygen, or nitrogen is of
particular interest
 Because of the small size of the hydrogen atom and its large electrostatic
field, it can move in close to an electronegative atom and form an
electrostatic type of union known as a hydrogen bond or hydrogen bridge.
.
Hydrogen bonding
It accounts for many of the unusual properties of water including its high dielectric constant,
abnormally low vapor pressure, and high boiling point.

Several structures involving hydrogen bonds are shown in Figure below. The dashed lines
represent the hydrogen bridges. It will be noticed that intra- as well as intermolecular
hydrogen bonds may occur (as in salicylic acid)
PRACTICE EXERCISE
In which of the following substances is significant hydrogen
bonding possible: methylene chloride (CH2Cl2) phosphine
(PH3) hydrogen peroxide (HOOH), or acetone
(CH3COCH3)?

Answer: HOOH
Intermolecular
Forces
Bond Energy

Bond energies serve as a measure of the strength of bonds.


Hydrogen bonds are relatively weak, having bond energy of
about 2 to 8 kcal/mole as compared with a value of about 50 to
100 kcal for the covalent bond and well over 100 kcal for the
ionic bond
Summarizing Intermolecular Forces

Intermolecular
Forces
PRACTICE EXERCISE
(a) Identify the intermolecular forces present in the
following substances, and (b) select the substance with the
highest boiling point: CH3CH3, CH3OH, and CH3CH2OH.

Answers: (a) CH3CH3 has only dispersion forces, whereas the


other two substances have both dispersion forces and hydrogen
bonds; (b) CH3CH2OH

Intermolecular
Forces
Intermolecular Forces Affect Many
Physical Properties

The strength of the


attractions between particles
can greatly affect the
properties of a substance or
solution.

Intermolecular
Forces
Viscosity
• Resistance of a liquid to flow is
called viscosity.
• It is related to the ease with
which molecules can move past
each other.
• Viscosity increases with
stronger intermolecular forces
and decreases with higher
temperature.

Intermolecular
Forces
Bellwork-Intermolecular forces

List the following compounds in order of increasing intermolecular


forces.
HCOOH CH3COOH CH3(CH2)10COOH CH4 CH3CH3
formic acid acetic acid lauric acid methane ethane

Which compound should have the highest boiling point?


Which compound is most likely a gas at room temp?
Which compound should flow the slowest?

Intermolecular
Forces
Polymorphism is the property of having more than one crystalline form (crystal habits).
Solvents might get trapped in the crystalline lattice, creating solvate.
Crystal habit

• Crystal habit impacts the physical properties of a substance, such as flowability,


compaction, and dissolution rate, which are important in industries like
pharmaceuticals
• Solubility and melting points are very important in pharmaceutical processes, including
dissolution and formulation, explaining the primary reason we are interested in polymorphs.
Case study
 One high profile case of polymorphism was ritonavir, a peptidomimetic
drug used to treat HIV-1 infection and introduced in 1996.
 In 1998, ritonavir, which was marketed in a dissolved formulation until a
previously unknown, more stable and less soluble polymorph appeared
causing slowed dissolution of the marketed dosage form and
compromising the oral bioavailability of the drug.

 This even forced the removal of oral capsule from market and
reformulation of the product before it could be reintroduced to the market.
Crystal solvates exhibit a wide range of behavior depending
on the interaction between the solvent and the crystal
structure.
1. With some solvates, the solvent plays a key role in holding
the crystal together.
• For example: it may be part of a hydrogen bonded network
within the crystal structure.
• These solvates are very stable.
• They are difficult to desolvate (to remove the solvent).
• When these crystals lose their solvent  they collapse and
recrystallize in a new crystal form.
• They resemble polymorphic solvates
 2. In other solvates, the solvent is not part of the
crystal bonding. – It merely occupies voids in the
crystal.
These solvates lose their solvent more readily.
Desolvation does not destroy the crystal lattice.
This type has been called a pseudopolymorphic
solvate.
• For example: Spironolactone has two polymorphs
and four solvates.
– It depends on whether it is crystallized from
acetonitrile, ethanol, ethyl acetate or methanol.
– Each of these solvates is transformed to the
- The dissolution rates of solvates can vary
considerably.
- Differences in solubility and dissolution rate between
solvates can lead to measurable differences in their
bio availabilities.
Co Crystals
 Co-crystals are crystalline materials composed of two or more different molecules,
typically an active pharmaceutical ingredient (API) and a co-former, which are solid
at room temperature. These components are held together in a specific
stoichiometric ratio through non-covalent interactions like hydrogen bonds, van der
Waals forces, or ionic bonds.
 Co-crystals are used to modify and improve the physicochemical properties of an
API, such as solubility, stability, dissolution rate, and mechanical properties, without
altering the molecular structure of the API itself.
 Examples: A well-known example is a co-crystal of ibuprofen and
nicotinamide, which has improved solubility compared to pure ibuprofen.
 The objective for pharmaceutical cocrystals is to have properties that differ
from that expected of the pure APIs without making and/or breaking
covalent bonds
Preparation of amorphous materials

 In principle: most classes of material can be prepared in the


amorphous state …how? When the rate at which they are
solidified is faster than the rate at which their molecules can
align themselves into a crystal lattice with 3D order.
 • It is possible to convert crystalline material to amorphous
when supplying mechanical or thermal energy:
– Grinding and milling
– Compression
– Drying
 Some materials, notably polymers, such as poly(lactic acid),
PVP, PEG are inherently amorphous.
 • Even at very slow solidification rate  such large molecules
are often unable to form perfect crystals because of the
difficulty in arranging the chains of these flexible molecules in
an ordered manner:
 • They are often semicrystalline: contain areas of crystalline
nature surrounded by amorphous regions.
• This process is widely used in the pharmaceutical industry
for the preservation and stabilization of therapeutic
agents like vaccines, proteins, peptides, antibiotics, and
other sensitive biologics that are prone to degradation
when exposed to moisture or heat

You might also like