PHYSICO-CHEMICAL PROPERTIES OF

DRUGS

Exercise No. 1

PHYSICO-CHEMICAL PROPERTIES OF DRUGS

Physical Chemical

Solubility and Permeability Partition Coefficient

Physical State Isomerism

Polarity Intermolecular Forces

Particle Size Ionization

Melting Point pH

Functional Group

PHYSICAL PROPERTIES

Solubility

first requirement for drug

absorption

• less or no solubility yields

minimal or no

response/effect from the

drug

Permeability

way how substances

“travel through” cellular

membranes

• poor permeability can

lead to poor absorption

across the GI mucosa or

poor distribution

throughout the body

PHYSICAL PROPERTIES

Solid Dosage Form

Solid Drug Particles

Drug in solution at

absorption site

Drug in the body

disintegration

dissolution

permeation

PHYSICAL PROPERTIES

Drug Classification according to Solubilty/Permeability

Class Solubility Permeability Absorption

Pattern

Rate Limiting

Step

Example

I High High Well absorbed Gastric

Emptying

Diltiazem

II Low High Variable Dissolution Nifedipine

III High Low Variable Permeation Insulin

IV Low Low Poorly

absorbed

Case by

case

Taxol

PHYSICAL PROPERTIES

Physical State

solid drugs needs to dissociate to exert its effect, thus it

will take time to elicit a response compared to a drug in

liquid form.

PHYSICAL PROPERTIES

Physical State

Order of Absorption

Modified Release Tablets

Enteric Tablets

Coated Tablets

Compressed Tablets

Capsules

Suspensions

Emulsions

Solutions

PHYSICAL PROPERTIES

Polarity

“LIKE DISSOLVES LIKE”

To get across most membranes, the drug must be

relatively NON-POLAR (lipophilic)

To be soluble in water, a drug must be POLAR

(hydrophilic)

PHYSICAL PROPERTIES

Particle Size

smaller particle size

higher dissolution rate

faster absorption

Melting Point

lower melting point

faster absorption

CHEMICAL PROPERTIES

Partition Coefficient

for a drug to be orally absorbed, it must pass through

lipid bilayers in the intestinal mucosa.

low lipid solubility

poor absorption

CHEMICAL PROPERTIES

Isomerism

drug molecules must generally interact with

biomolecules (enzymes/receptors) in a very SPECIFIC

way to elicit a pharmacological response

many drugs are optically active and have different

actions in relation to its spatial arrangement

CHEMICAL PROPERTIES

Constitutional Isomers

Pentobarbital

(short-acting)

Amobarbital

(intermediate-acting)

CHEMICAL PROPERTIES

Enantiomers

(R) Isomers

(R) Naproxen (inactive)

(S) Isomers

(S) Naproxen (NSAID)

CHEMICAL PROPERTIES

Diastereomers

Cis Isomers

- Only 7% active

Trans Isomers

- Estrogenic

CHEMICAL PROPERTIES

Geometric Isomers

E Isomers Z Isomers

Clomiphene - Ovulation Stimulant

CHEMICAL PROPERTIES

Diastereomers

Dextrorotatory Isomers

Dextrorphan

(anti-tussive)

Levorotatory Isomers

Levorphanol (analgesic)

CHEMICAL PROPERTIES

Intermolecular Forces

― drugs interact and bind to the binding sites

(receptors/proteins/enzymes) through intermolecular

forces

― relatively weak forces must be involved in the drug-

receptor complex yet be strong enough that other

binding sites will not competitively deplete the site of

action

CHEMICAL PROPERTIES

Intermolecular Forces

covalent bonds – long lasting or irreversible effects are

desired. e.g. antineoplastic agents, antibacterials

ionic bonds

hydrogen bonds

Van der waals forces

dipole-dipole

ion-dipole

hydrophobic bonds

Reversible; Desired bonds for most

drugs

CHEMICAL PROPERTIES

pH

most drugs are weak acids and weak bases

an acidic drug dissolves in a basic medium

a basic drug dissolves in an acidic medium

pH in different body compartments

Plasma 7.35 – 7.45

Buccal Cavity 6.2 – 7.2

Stomach 1.0 – 3.0

Duodenum 4.8 – 8.2

Jejunum and ileum 7.5 – 8.0

Colon 7.0 – 7.5

CHEMICAL PROPERTIES

Ionization

only the unionized form of a drug can partition through

membranes

the ionized form is more water-soluble (required for drug

administration and drug distribution in plasma)

CHEMICAL PROPERTIES

Ionization

ionized drug

high solubility

high absorption

low lipid solubility

unionized drug

high permeability

low polarityhigh lipid solubility

CHEMICAL PROPERTIES

Functional Group

Phase I and II reactions

addition of polar functional groups results in more water

soluble and readily excretable metabolites

QUESTIONS

1. What are the requirements for a drug to exert its

biological effect?

The Drug must:

pass through barriers

survive alternate sites of attachment/storage

avoid metabolic destruction before it reaches the site of

action

allow favorable binding characteristics

dissociate from receptor and reenter the systemic

circulation to be excreted

QUESTIONS

2. What route of administration will give fast drug

action?

Intravenous (IV) route of administration

QUESTIONS

3. What are the different forces involved in drug-

receptor interaction? Explain.

Covalent Bonds – bond formed by sharing electrons

between atoms

Ionic Bonds – bond formed by the attraction between

atoms of opposite charge

Hydrogen Bonds – bond formed by hydrogen atoms

bound to electronegative atoms

QUESTIONS

3. What are the different forces involved in drug-

receptor interaction? Explain.

Ion-Dipole – bond formed from the electrostatic

attraction between an ion and a neutral molecule that

has a dipole.

Dipole-Dipole – bond formed between the positive end

of one polar molecule and the negative end of another

polar molecule

Van der waals forces – bond formed when any two

uncharged atoms approach each other very closely

QUESTIONS

4. What form of drug is well absorbed and excreted

in the body?

Intravenous (IV) route of administration

QUESTIONS

5. What is the importance of a drug receptor? What

is the principle of Drug-Receptor Interaction?

DRUG RECEPTORDRUG-RECEPTOR

COMPLEX

PHARMACOLOGICAL

EFFECT