PPFA 7- states of matter and their transformation

What are the 3 state of matters ?

Three primary states : solid, liquid and gases

why are these important - help to understand pharmaceutical formulation , stability and packaging 

What are some examples of medications in these states and their properties ?

What are intermolecular forces ?

-Secondary forces between molecules, weaker than covalent/ionic bonds.

-These forces also critically affect the structure and stability of biomolecules (e.g.,
proteins, DNA) in pharmaceutical and biotech applications.

-Types of intermolecular forces vary in strength and pharmaceutical impact.

What are intermolecular forces essential for ?

Essential for:
Drug formulation → tablet compression, powders, aerosols.
Drug delivery → solubility and dissolution control.
Stability → solid-state polymorphism and amorphous stability.

What is are repulsive vs attractive forces?

Molecules experience two opposing forces :

Attractive - hold molecules together 

Repulsive - prevent collapse 

Describe a repulsive forces

When two particles approach, their electric double
layers overlap, causing repulsion

What is the pharmacy relevance of repulsive forces ?

Pharmacy relevance:
Stabilizes colloidal drug suspensions (e.g.,
emulsions, liposomes).
Prevents aggregation of particles in
formulations.

When does repulsion dominate?

At Very Short Distances
Repulsion dominates strongly
-This creates an energy barrier that prevents
particle aggregation

Describe a attractive forces

Attractive Forces dominates at intermediate
distance → Molecules are pulled closer

What is the relevance of attractive forces ?

Pharmacy relevance:
Promotes aggregation if repulsive forces are
weak.
Important for powder compaction in
tablets and aerosol stability.

Note- energy approx. 0 = no significant interaction

What do these forces control?

These forces control physical properties
like:
Melting and boiling points
Density
Solubility
Vapor pressure

What is Van der waals ?

Weak intermolecular forces that relate to non ionic interactions between molecules,yet they involve charge – charge interactions.

Partial charges can be permanent or be induced by neighbouring groups

What are the types of van der waals forces?

Types of Van der Waals Forces:

Keesom Forces (Dipole–Dipole)
Debye Forces (Dipole-Induced Dipole)
London Dispersion Forces (Induced Dipole-Induced Dipole)

What is a keesom forces and describe it ( dipole - dipole ) ?

Occur between permanent dipoles in polar molecules.

The permanent dipoles interact
with one another in an ion-like
fashion.

Because the charges are partial,
the strength of bonding is much
weaker

What is the pharmaceutical relevance of keesom forces?

Pharmaceutical Relevance

Solubility: Polar drug molecules dissolve better in
polar solvents.
Tablet stability: Dipole interactions between
excipients help with powder compaction

What is debye forces ( dipole - induced dipole)

A permanent dipole induces polarity in a nearby non-polar molecule, creating attraction

Show the ability of a permanent
dipole to polarize charge in a
neighbouring nonpolar easily
polarizable molecule.

What is london dispersion forces ( induced dipole- induced dipole) ?

Caused by temporary dipoles due to fluctuations in electron distribution.

why is it important - Important in non-polar molecules like
hydrocarbons and biological membranes

What is orbital overlap ( π - π  interactions) ?

-type of dipole - dipole force

-the interaction between π electron orbitals in systems

eg - aromatic-aromatic interactions can occur when the double bonded π -orbitals from two rings overlap 

Whta is a hydrogen bond ?

-The interaction between H
and highly electronegative
atoms (O, N, F)

• stronger than van der waals stronger

What is the applications of hydrogen bonds in pharmacy ?

Applications in pharmacy:
• Improves solubility of polar
drugs.
• Stabilizes crystalline forms.
• Governs polymorphism → affects
bioavailability.

What is the ion - dipole and ion- induced dipole forces ?

Occur between polar or nonpolar molecules and ions
Example - Ion-induced dipole forces
are involved in the formation of the
iodide complex.

What is the role of ion- dipole?

ion-Dipole
▪ Major role in dissolution of
salts.
▪ Example: NaCl dissolving in
water.

This effect can clearly influence the solubility of solute and play
important role in dissolution process

What is ion-ion interaction?

Strongest interaction.
Relevant for salt forms of drugs to enhance stability and solubility.

Intermolecular interactions - summary

What is gibbs phase rule ?

This rule tells us how many variables we can control while maintaining equilibrium, which
is key when formulating stable products:

F = C − P + 2

F = degrees of freedom — how many variables we can change independently
C = number of components,
P = number of phases in equilibrium

What is gibbs phase rule - single component

If we have liquid water only (P=1, C=1) ⟶ What is F?
we can vary both temperature and pressure freely
F = 2

What is gibbs phase rule - two components ?

f we have liquid + vapor (P = 2, C=1) ⟶ What is F?
we can only change one variable without disturbing equilibrium
F = 1

What is gibbs phase rules- 3 components ?

At the triple point (solid + liquid + vapor, P = 3, C=1) ⟶ What is F?
we can't change anything without shifting the phases
This is why the triple point of water has a fixed temperature and fixed pressure
F = 0

Phase diagram

What is a phase diagram ?

Phase diagrams show relationships between
temperature, pressure, and composition

What is phase equilibrium ?

Phase equilibrium: stable coexistence of
phases without net change.
Pharmacy relevance:
▪ Predict drug stability & storage conditions
▪ Guide formulation development
▪ Understand solubility & melting behavior

What is freeze - drying ( lymphilization) ?

Direct transition from solid - gas without becoming liquid

used in pharmaceuticals for dry heat - sensitive materials

What is the process for freeze drying ?

Process-

material is frozen

placed under vacuum

ice sublimes, leaving dry product

Advantages - preserves structure , stability and potency of drugs

Scenario - application 

A batch of a monoclonal antibody arrives ,but its stored as a freeze-dried powder ( lyophilized vial) instead of a liquid .

antibody - biologic

-protein = can denature

-solid - more stable than liquid ,limited in conditions ,stable longer

-heat sensitive - FD better method so convert S-G ( avoid high temp)

-Before given - reconstituted with sterile water 

-Extended shelf life 

How do pharmaceutical solids exist ?

• solids exist as crystalline or amorphous forms ( or a combination of both)

What is a amorphous solids?

• irregular arrangement , higher solubility but lower stability

( easily changes overtime)

What is a crystalline solid ?

• highly ordered , definite melting points - more sharp melting points ,to break all of these bonds 

• crystals - with weak forces have low melting points

• crystals with strong lattices ( ie strong attractive forces) have high melting points

How do crystals form?

Two main routes:
Cooling molten material (e.g. suppositories, creams)
From solution → requires supersaturation 

Ways to induce crystallization from solution:
Evaporation (↑ concentration)
Cooling (↓ solubility)- enhanced by heating ,than cooling might leave some crystals 
Antisolvent addition (↓ solubility)

Crystal formation steps:
Nucleation (first tiny cluster)
Growth (molecules add on)

Crystallization = supersaturation → nucleation → growth → ordered solid

What is the main crystallization equation?

Crystallization = supersaturation → nucleation → growth → ordered solid

What is polymorphism?

Polymorphism is the ability of a substance to exist in multiple crystalline forms, each with different properties

What is pharmaceutical importance of polymorphism  ?

Pharmaceutical importance:
• Affects solubility, dissolution, and bioavailability.
• Impacts drug formulation and stability.
Polymorphs will convert to the stable form over
time.
Regulatory authorities require control of
polymorphs primarily for this reason

What links polymorphism and tablet manufacture ?

Polymorphs affect not just dissolution but also
physical properties

Paracetamol: high-dose drug with poor
compression → difficult to make tablets
Limited excipient can be added (tablet size
constraint)

Researchers explore alternative polymorphs
with better compressibility to improve tablet
manufacture

What is a hydrate crystals ?

Hydrate = crystal lattice with water molecules trapped in fixed
ratio (e.g. monohydrate, dihydrate).
~11% of known compounds exist as hydrates.
Most common: monohydrate > dihydrate > trihydrate

What is solvate crystals  ?

Solvate = lattice contains other solvents (e.g. ethanolate).
Rarely used in pharma (risk of toxicity/impurity).

What are some properties of hydrates ?

Hydrates can behave like polymorphs
(“pseudopolymorphism”).

What is the effect on dissolution rate (solubility)?

Dissolution rate may be faster or slower than anhydrous
form:
Theophylline: anhydrous dissolves faster
(supersaturated → reverts to hydrate equilibrium).
Erythromycin: hydrates dissolve faster (water
disrupts lattice).
Key point: Hydrate vs anhydrous form changes dissolution and bioavailability, so must be
carefully controlled in drug development