PHYSICAL PHARMACY

physical pharmacy

Deals with the principles underlying the development of a successful dosage form

pharmaceutics

Is a branch of pharmaceutical sciences that deals with Investigations of physical and chemical properties of drug molecules

drug

agent or substance intended for use in the diagnosis, cure, mitigation, treatment and prevention of disease

dosage form

form suited for administration to the patient

drug product

a finished dosage form that contains an active drug ingredient (palatable, convenient, safe, and effective)

binding forces between molecules

Forces that hold atoms, ions, or molecules together.

intramolecular forces

forces “within” molecules or compounds hold atoms together and are generally stronger

• Ionic Bonds

• Covalent Bonds

• Metallic Bonds

• Hydrogen Bonds

INTRAMOLECULAR FORCES (4)

• Pure Covalent Bonds | < 0.4

• Polar Covalent Bond | 0.4 -1.7 (2.0)

• Ionic Bonds | >1.7 (2.0)

Intramolecular Bonds EN Difference (3)

Intermolecular Forces

forces “between” molecules

1. Van der Waals Forces

2. Ion-Dipole

3. Ion-Induce dipole Interaction

4. Hydrogen bonds

Intermolecular Forces (4)

1. Keesom Forces

2. Debye Forces

3. London Forces

Van der Waals Forces (3)

Keesom forces

oriantation/allignment effecf

Debye force

induction effect (force)

London forces

Dispersion effect (force)

London force

force of hexane

Debye force

force of ether

London Forces

force of CCl4

Keesom forces

Force or water

keesom forces

force of alcohol

keesom forces

force of acetone

debye forces

force of ethylacetate

debye forces

dipole-induced dipole forces

London forces

induced dipole - induced dipole forces

Ion-Dipole Forces

(+/-) charged ion + polar forces

ion-induced dipole

(+/-) charged ion + nonpolar forces

tri-iodide

iodine + KI = formation of __ complex

ion-dipole forces

(force) quaternary ammonium + tertiary amine

ion-induced dipole force

(force) iodine + KI

hydrogen bonds

Interaction between molecules containing Hand highly EN atom (F, S, O, N)

• water

• alcohol

• carboxylic acids

• esters

• aldehyde

• NOT ethers and ketones

hydrogen bonds examples

hydrogen bonds

Responsible for unusual properties of water

• high dielectric constant (universal solvent

• abnormally low vapor pressure

• high boiling point

unusual properties of water

• __ dielectric constant (universal solvent

• abnormally __ vapor pressure

• __ boiling point

In proteins: a helices, b sheets

• In nucleic acids: DNA (A-T and G-C)

note: A-T has 2 HB, G-C has 3 HB

HYDROGEN BONDS can also exist intramolectularly

• in proteins: __

• in nucleic acids: DNA (___ bonds)

1. Attractive Forces

2. Repulsive Forces

Manifestation of Intermolecular Forces

Polarity

Unequal distribution of electrons in a bond or molecule.

higher

___ Electronegativity difference = higher polarity

asymmetric

SYMMETRY OF THE MOLECULE

Polar molecules = ___ and have nonzero dipole moments

perfect

SYMMETRY OF THE MOLECULES

• Nonpolar molecules with __ symmetry = zero dipole moments

stronger = higher

The stronger IMFA = ___ interaction = __ BP, MP, viscosity, surface tension

London Dispersion Forces

IMF of Methane (CH4)

Dipole-Dipole Interactions

IMF of Chloromethane (CH3Cl)

Hydrogen Bonding

IMF of Methanol (CH3OH)

1. Additive

2. Constitutive

3. Colligative

PHYSICAL PROPERTIES OF DRUG MOLECULES

Additive

Derived from the sum of individual properties atoms or functional groups present in molecule

1. mass

2. molecular weight

3. volume

examples of additive property of molecules

constitutive

dependent on the structural arrangement of the atoms within the molecule

1. optical activity

2. surface tension

3. viscosity

4. boiling point

examples of constitutive properties of drug molecules

colligative

dependent upon the total number of non-volatile solute particles present im the solution

1. vapor pressure lowering

2. BP elevation

3. FP depression

4. osmotic pressure

examples of colligative properties of molecules

molar refraction

combined additive-constitutive property

ionization

gas to plasma

recombination

plasma to gas

Latent Heat/ Molar Heat

Heat necessary for of a gas, solid or liquid to change to another phase

fusion / melting

solid to liquid

absorbed; released

Heat __ to convert 1 mole of solid to liquid

Heat __ to convert 1 mole of liquid to solid

absorbed; released

Heat ___ to convert 1 mole of solid to gas

Heat ___ to convert 1 mole of solid to gas

absorbed; release

Heat __ to convert 1 mole of a liquid to gas

Heat __ to convert 1 mole of a gas to liquid

temperature

gas have kinetic energy affected by ___ that produces rapid motion

indirect; temperature

(Boyle’s gas law) Pressure and Volume has __ relationship at constant ___

Boyle’s Law

(gas law) Pressure and Volume has indirect relationship at constant temperature

Charles’ Law

(gas law) Volume and Temperature has direct relationship at constant pressure

direct; pressure

(Charles’ gas law) Volume and Temperature has __ relationship at constant __

Gay-Lussacs Law

(gas law) Pressure and Temperature has direct relationship at constant volume

direct; constant

(Gay-Lussacs gas law) Pressure and Temperature has __ relationship at constant __

Combined Gas Law

PV =nRT

Ideal Gas Law

R = 0.08205 liter atom/mol K

R = 8.314 × 10^6

molar gas constant (R)

Real Gas Law or Van der Waals

Avogadro’s Law

(gas law) states that equal volume of mass at the same temperature and pressure contain the same number of molecules

6.02 x 10²³

Avogadro’s number

Graham’s Law

(gas law) The speed of diffusion of a gas is relative to the molecular weight or density of the gas.

Henry’s Law

(gas law) the solubility of a gas is directly proportional to the pressure at constant temperature

Dalton Law of Partial Pressure

(gas law) The total pressure of system (P) is the sum of individual partial pressure of each component.

Raoult’s Law

(gas law) The partial vapor pressure of each volatile constituent is equal to the vapor pressure of the pure constituent multiplied by its mole fraction in the solution

Clausius-Clapeyron

(gas law) The relationship between the vapor pressure and the absolute temperature of a liquid

Kinetic Molecular Theory

theory that explains the behavior of gases and supports the validity of gas laws

Kinetic Molecular Theory

theory that explains the behavior of gases and supports the validity of gas laws

• the volume of a particle is almost zero

• the particles do not attract one another

• KE is directly proportional to K

• the molecules exhibit pefect elasticity

KINETIC MOLECULAR THEORY

• the volume of a particle is __

• the particles __ one another

• KE is __ proportional to K

• the molecules exhibit __

Real Gas or Van der Waals Equation

(law) Real gases are not composed of infinitely small and perfectly elastic non-attracting spheres.

finite; attract

REAL GAS LAW

• Real gases molecules have __ volume, and tend to __ one another

decreases

LIQUEFACTION OF GAS

Gas ￫ loss of KE (cool) ￫ velocity __

Critical temperature

temperature above which liquid no longer exist

Critical pressure

pressure required to liquefy a gas at critical temperature

CT= 374C or 647K

CP= 218 atm

CT and CP of water

CT= 5.2K

CP= 2.26 atm

CT and CP of Helium

aerosols

only true tamper resistant container

propellant + concentrate

aerosol=

Vapor pressure

is the pressure exerted by vapor molecules above a liquid when liquid molecules with the higher KE and proximity to a surface break away from the surface of the liquid and pass into the gaseous state

low; low

VAPOR PRESSURE OF LIQUID (at low temperature)

- Liquid molecules have __ kinetic energy.

- Only a few molecules can escape from the liquid surface.

- Therefore, vapor pressure is __.

gain; escape; increase

VAPOR PRESSURE OF LIQUID (as temperature increases)

- Molecules __ more kinetic energy.

- More molecules __ from the liquid and became vapor

- therefore, the number of vapor particles increases

- this causes vapor pressure to __

evaporation and condensation

In a closed container, these two processes eventually reach dynamic equilibrium.

equal

A liquid boil when its vapor pressure becomes __ to atmospheric pressure

equals

boiling point is the point when the vapor pressure __ atmospheric pressure

increase; decrease

HYDROCARBONS

higher MW (longer chain) = __ BP

branching = __ BP

low BP

NONPOLAR MOLECULS

• weak London forces = _ BP

high

POLAR MOLECULES

strong H-bonds = __ BP

1. crystalline

2. amorphous

3. polymeric

types of solid

crystalline

(type of solid) fixed geometric pattern

amorphous

(type of solid) randomly arrange molecules