LESSON #2: STATES OF MATTER RELATED TO PHARMACEUTICAL FORMULATIONS

Cohesive forces

Type of forces where like molecules are attracted to each other (e.g., water to water)

Adhesive forces

Type of forces where different molecules are attracted to one another (e.g., water to beaker)

Lennard-Jones Potential Graph

A model that describes that as two molecules approach each other (at a moderate distance), the energy changes are gradual and negative (attractive) to a point where a minimum in the potential energy occurs.

Increasing exponential graph from negative to 0

When molecules are far apart, they start to approach each other, meaning attractive forces start to form to a point where a minimum in potential energy occurs. There is an increase in negative potential energy.

Describe how this looks on a graph.

Decreasing exponential graph from positive to 0

As the energy starts rising rapidly (due to the attractive forces) as the intermolecular distances become smaller, repulsive forces begin to dominate, meaning resistance is starting to form. There is an increase in positive potential energy.

Describe how this looks on a graph.

1. Attraction

2. Repulsive

The Lennard-Jones Potential graph shows how the energy between two molecules changes as the distance between them changes. It basically says that at:

1. Far distance, there is _______ forces, while at

2. Close distance, there is _______ forces.

Potential energy

It is the energy stored in an object.

Keesom forces

Other name for Dipole-dipole forces.

Debye forces

Other name for Dipole-induced dipole forces.

London Dispersion forces

Other name for Induced dipole-induced dipole forces.

1-7 kcal/mol

Van der Waals Forces: Energy (kcal/mol) of Dipole-dipole (Keesom forces)

1-3 kcal/mol

Van der Waals Forces: Energy (kcal/mol) of Dipole-induced dipole (Debye forces)

0.5-1 kcal/mol

Van der Waals Forces: Energy (kcal/mol) of Induced dipole-induced dipole (London forces)

protein secondary structure (α–helices)

Van der Waals Forces: Dipole-dipole (Keesom forces) stabilize __________________.

effect on states of matter

Van der Waals Forces: Dipole-induced dipole (Debye forces) stabilize ________________.

1. liquefaction

2. dipole interactions

3. bonding

Van der Waals Forces: Induced dipole-induced dipole (London forces), causes ___________ of gases, molecular _______________ in solubility, complexation, and other physical _________ phenomena

H₂O, HCl, alcohol, acetone, phenol

Examples of Dipole-dipole (Keesom forces)

ethyl acetate, methylene chloride, ether

Examples of Dipole-induced dipole (Debye forces)

1-7 kcal/mol

Ion-dipole Forces: Energy (kcal/mol) of Ion-dipole

Quaternary ammonium ion with tertiary amine

Examples of Ion-dipole

pharmaceutical salts

Ion-dipole Forces: Ion-dipole acts as ________________.

KI (enhance solubility) + iodine

Examples of Ion-induced dipole

ionic crystalline subs

Ion-induced dipole has a solubility of _________________ in H₂O.

Hydrogen Bonding

Intermolecular Attractive Forces: Attraction of a hydrogen atom for a strongly negative atom

Hydrogen Bonding

Applications of _____________ protein α–helix and β–sheet structures, conformation of proteins, physical properties of alcohols compared to alkanes; carboxylic acids compared to esters, aldehydes, and ketones; sugars.

Hydrophobic interaction

Intermolecular Attractive Forces: forces of attraction between nonpolar atoms and molecules in water

Hydrophobic interaction

Applications of _______________ are its structure stabilizes molecules including proteins and bilayer membrane structures.

Gas

States of Matter:

1. no regular shape; capable of filling available space

2. higher kinetic energy; weak intermolecular forces

3. compressible

Liquid

States of Matter:

1. occupies a definite volume; takes the shape of the container

2. denser and possesses less kinetic energy than gases

3. less compressible than gases more compressible than solids

Solid

States of Matter:

1. Have a fixed shape

2. strong intermolecular forces, little kinetic energy

3. nearly incompressible compared to other states

Ideal Gas Law

Gas: Equational law that is useful in calculating properties of gases at atmospheric pressure and at temperatures above their boiling points.

PV = nRT

Gas: The ideal gas law equation has variables that are directly proportional to each other. What is the equation?

Boyle’s Law

Gas: States that volume is inversely proportional to pressure.

Charles’ Law

Gas: States that volume is directly proportional to temperature.

Avogadro’s Law

Gas: States that volume is directly proportional to the number of moles

Partial Pressure

Gas: The higher the concentration, the higher the __________________.

Henry’s Law of Gas Solubility

Gas (Blood gases, oxygen and carbon dioxide): Law that states that the amount of gas dissolved in the plasma is proportional to the partial pressure of the gas in equilibrium with the plasma

Dalton’s Law of Partial Pressures

Gas (Blood gases, oxygen and carbon dioxide): Law that states that the partial pressure is the pressure a gas would exert if it alone occupied the whole volume of the mixture

Vapor Pressure

Liquids: pressure exerted by a vapor in thermodynamic equilibrium with its liquid or solid phase in a closed system at a given temperature.

directly

Liquids (Vapor Pressure): Vapor pressure and temperature are ____________ proportional.

inversely

Liquids (Vapor Pressure): Vapor pressure and boiling point are _____________ proportional.

inversely

Liquids (Surface Tension): Surface tension and temperature are ______________ proportional.

Surface Tension

Liquids: the measure of force per unit length.

crystalline, polymeric, and polymorphs

Solids: The three types of solids are __________, __________, and __________.

1. Cubic

2. Sodium chloride

What do you call this crystalline solid? Give an example.

1. Tetragonal

2. Urea

What do you call this crystalline solid? Give an example.

1. Orthorhombic

2. ritonavir Form II

What do you call this crystalline solid? Give an example.

1. Rhombohedral

2. iodine

What do you call this crystalline solid? Give an example.

1. Hexagonal

2. iodoform

What do you call this crystalline solid? Give an example.

1. Monocyclic

2. sucrose, and ritonavir Form 1

What do you call this crystalline solid? Give an example.

1. Triclinic

2. Boric acid

What do you call this crystalline solid? Give an example.

three-dimensional lattice

Solids: Molecules or atoms are arranged in repetitious _______________ units (unit cell) infinitely throughout the crystal

Atom to atom

Type of Crystal Bonding described below:

1. Example: Carbon, diamond

2. Bonding: Strong carbon covalent bonds

3. Physical Characteristics: Hard, large crystals

Metallic

Type of Crystal Bonding described below:

1. Example: Silver

2. Bonding: Strong metal bond

3. Physical Characteristics: Positive ions in a field of freely moving electrons

Molecular

Type of Crystal Bonding described below:

1. Example: Menthol, paraffin

2. Bonding: Van der Waals forces

3. Physical Characteristics: Close packing, weakly held together, low melting point

Ionic

Type of Crystal Bonding described below:

1. Example: NaCl

2. Bonding: Electrostatic ionic bond

3. Physical Characteristics: Hard, close packing, strongly held together, high melting point

Polymorphs

Solids: type of solid structure that may exist in more than one crystalline structure

intermolecular bonding patterns, conformational changes, and molecular orientations

Changes in Crystalline Forms include _________________, _____________, and ________________.

1. Melting point

2. Solubility

3. Stability

Physical properties included in polymorphs.

3

Polymorphic (# of Forms): Acetaminophen

2

Polymorphic (# of Forms): Caffeine

2

Polymorphic (# of Forms): Phenobarbital sodium

2

Polymorphic (# of Forms): Phenytoin

4

Polymorphic (# of Forms): Chloramphenicol palmitate

3

Polymorphic (# of Forms): Cimetidine

2

Polymorphic (# of Forms): Nifedipine

2

Polymorphic (# of Forms): Progesterone

2

Polymorphic (# of Forms): Theophylline

Hydrate

Solvates and Hydrates: Form where water is included in a lattice, commonly USED as a drug substance. It is less soluble in water or aqueous mixtures than anhydrous forms

Solvate

Solvates and Hydrates: Form that is incorporated into the lattice. It is NOT chosen as drug substances due to possible toxicity of common solvents.

Salt crystals

Solvates and Hydrates: A lattice accommodating other molecules to form salts. It is when two (2) ionized compounds will interact with the lattice to form a crystalline salt.

Cation/Counterion

Salt crystals: the corresponding compound in a salt. Its properties include melting point, stability, solubility, dissolution, bioavailability.

53.4 %

Common Counterions (Anion): Frequency of Hydrochloride

7.5%

Common Counterions (Anion): Frequency of Sulfate

4.6%

Common Counterions (Anion): Frequency of Bromide

4.2%

Common Counterions (Anion): Frequency of Maleate

4.2%

Common Counterions (Anion): Frequency of Mesylate

3.8%

Common Counterions (Anion): Frequency of Tartrate

3.3%

Common Counterions (Anion): Frequency of Acetate

2.7%

Common Counterions (Anion): Frequency of Citrate

2.7%

Common Counterions (Anion): Frequency of Phosphate

75.3%

Common Counterions (Cation): Frequency of Sodium

6.9%

Common Counterions (Cation): Frequency of Calcium

6.3%

Common Counterions (Cation): Frequency of Potassium

2.9%

Common Counterions (Cation): Frequency of Meglumine

1.7%

Common Counterions (Cation): Frequency of Tromethamine

1.2%

Common Counterions (Cation): Frequency of Magnesium

1.2%

Common Counterions (Cation): Frequency of Zinc

0.6%

Common Counterions (Cation): Frequency of Lysine

0.6%

Common Counterions (Cation): Frequency of Diethylamine

Cocrystals

Homogeneous multicomponent phase of fixed stoichiometry where the chemical entities are held together in a crystal lattice by intermolecular forces.

water and solvents

Cocrystals also contain _______ and ______ to form cocrystalline hydrates

ionizable group

Cocrystals are a good option to change properties when an ___________ is not available

Amorphous solids

Solids: No long-range order over many molecular units to produce a lattice or crystalline structure

1. Glasses: nonequilibrium solid form

2. Supercooled liquids: viscous equilibrium liquid form

Amorphous solids:

1. Glasses: _________________ form

2. Supercooled liquids: ________________ form

Do not

Amorphous solids do or do not possess melting points?

Glass transition (Tg) temperature

temperature where an amorphous material converts from a glass to a supercooled liquid upon heating

1. less

2. more

Amorphous solids are _____ physically stable but _____ soluble than crystalline materials

surfactants

An amorphous drug is stabilized by a polymer or a combination of polymers or ___________

Surfactants

Also referred to as surface-active agents. When they are placed in a solution, they will act at the boundary of two materials or two states of matter