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LIBERATION
Entails the release and
dissolution of the drug

The more soluble and


permeable the drug, the
faster will be the absorption
thus, greater bioavailability
and hence, the faster
response from the body.

DRUG FORMULATION
Active Pharmaceutical
Ingredient (API)
Pharmaceutical
Excipients/ Adjuvants

EXCIPIENTS
The raw materials,
whose desirable
properties or the lack
thereof, will affect the
final drug product.

ACTIVE PHARMACEUTICAL
INGREDIENT (API)
The drug molecule that the
manufacturer intends to
deliver at the intended
site of action to produce
the effects.

DISSOLUTION
The rate-limiting step
for bioavailability

DRUGS CHEMICAL
STRUCTURE
Dictates the solubility
patterns of the drug in
aqueous solution and in
the different solvents

THE DRUG SHOULD


BE
Non-polar
(Lipophilic/Hydrophobic) to
traverse through membranes
Polar
(Nonlipophilic/Hydrophilic) to
dissolve in the aqueous
gastric juice

LIPID:WATER PARTITION
COEFFICIENT
Also called Partition
constanct
An in vitro test that provides
the ratio of the solubility of
a drug compound between
two immiscible solvents

Partition (P) = [Drug (non-ionized) in the organic


phase]
Coefficient
phase]

[Drug (non-ionized) in an aqueous

*The higher the P, the more lipophilic is


the drug, and assumed to behave with a
higher rate of diffusion through
membranes.

PH AFFECTS SOLUBILITY
AND THUS
BIOAVAILABILITY

DRUG STABILITY
Examples of Modifications done:
Using the salt form of the drug
molecule
Using dark, amber packaging
containers for light sensitive
drugs
Using the dry powder form of the
drug product which will be
reconstituted only before use
Minimizing exposure to moisture
Storage at 30C or lower
temperatures

CHIRALITY AND
SOLUBILITY
CHIRALITY the presence of
non-superimposable mirror
images of a compound
- also called stereoisomerism/
enantiomerism

DEXTROROTATORY
Rotates a plane of
polarized light to a
clockwise rotation
d-isomer
(+)-enantiomer

LEVOROTATORY
Counter-clockwise
direction
l-isomer
(-)-isomer

R- AND S- SYSTEM
S- (Sinister is Latin for left)
counter-clockwise
direction
R- (Rectus is Latin for
right) clockwise
direction

Chirality

RACEMIC MIXTURE
Occurs if the enantiomers
are present in a 50/50
ratio (no optical activity
due to cancellation)
Also known as
Racemate
Ex: Omeprazole,
Ibuprofen, Nicardipine,
Amlodipine

PHYSICAL PROPERTY
Solid drugs can be:
Crystalline form the
molecules are arranged in a
regularly repeating pattern
Amorphous consists of
disordered arrangement of
molecules and does not
possess a distinguishable
lattice characteristics

AMORPHOUS
Has greater solubility
than crystalline
Cannot be used in the
manufacture of drugs
because of stability
issues

POLYMORPHISM
The ability of the drug substance
to exist as two or more crystalline
forms that have different
arrangements of the molecules
within the crystal lattice
Affects the final drug product in
terms of dissolution, stability and
bioavailability

SOLVATES AND
HYDRATES
SOLVATES the result of the
interaction between the
solute and the solvent
forming a complex
Are crystalline solid adducts
containing a solvent
incorporated within the
crystal structure
Ex: Griseofulvin-Benzene
Solvate

HYDRATES If the
incorporated solvent is
water
Ex: Amoxicillin trihydrate

DELIQUESCENT
A substance that absorbs
water from the environment
and dissolves in it

HYGROSCOPIC
Absorbs water from the
environment but does not
dissolve in it

ANHYDROUS
SUBSTANCE

A compound that lost its


water to the environment

COMPLEXATION: SOLID
SOLUTIONS AND
EUTECTIC MIXTURES

EUTECTIC MIXTURE
The combination of two or more
compounds will result in a
mixture that will have a
different melting point than
the individual compound
Ex: EMLA

MANUFACTURING
FACTORS
How does the dosage form
affect the liberation of a drug
compound and ultimately,
affect the bioavailability and
drug action?

PARTICLE SIZE
Reducing particle size can
increase the surface area of
the molecule exposed to the
solvent (GIT fluid) resulting in
an increased dissolution rate

PROBLEMS
Highly lipophilic drugs
Dissolution is not the ratelimiting step
Faster dissolution will result
in faster decomposition of the
drug compound

PHARMACEUTICAL
ADJUVANTS

Should be inert
Can affect the formulation by:
1.Affect the performance of the
active pharmaceutical
ingredient in terms of
bioavailability
2.Can cause allergic reactions
to susceptible individuals

TABLETS
1.Diluents/ Fillers
2.Disintegrants
3.Binders
4.Lubricants