1 lab physico-chemical_properties_of_drugs[1]
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Transcript of 1 lab physico-chemical_properties_of_drugs[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
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