DRUG DELIVERY AND
TARGETING
Drug Delivery and Targeting Systems

It is dosage form or device that serve as drug
carrier to deliver the drug into targeted site
upon
application
using
suitable
rout
of
administration.

Drug
delivery
and
targeting
systems
referred to as:
"controlled release“
"sustained release"
"zero-order“
"membrane-controlled“
"monolithic"
"smart“
"stealth“
"reservoir"
are
Terminology of Drug Delivery and
Targeting Systems

Prolonged/sustained release:
The delivery system prolongs therapeutic
levels of the drug in blood or tissue for an
extended period of time.

Zero-order release:
The drug release does not vary with time;
thus the delivery system maintains a
(relatively) constant effective drug level in
the body for prolonged periods.

Variable release:
The delivery system provides drug input at a variable
rate, to match, for example, endogenous circadian
rhythms, or to mimic natural biorhythms.

Bio-responsive release:
The system modulates drug release in response to a
biological stimulus (e.g. blood glucose levels triggering
the release of insulin from a drug delivery device).

Modulated/self-regulated release:
The system delivers the necessary amount of drug
under the control of the patient.

Rate-controlled release:
The system delivers the drug at some predetermined rate, either systemically or locally,
for a specific period of time.

Targeted-drug delivery:
The delivery system achieves site-specific drug
delivery independent on site and rout of
administration

Temporal-drug delivery:
The control of delivery to produce an effect in a
desired time-related manner.

Spatial-drug delivery:
The delivery of a drug to a
specific region of the body
(dependant on both route
of administration and
drug distribution).

Bioavailability:
The rate and extent at
which a drug is taken up
into the body.
Advantages of controlled-release system
1. Improve patient compliance.
2.
Use of less total drug.
3. Fewer local or systemic side effects.
4. Minimal drug accumulation with long-term
dosage.
5. Fewer problems with potentiation or loss of
drug activity with long-term use.
6. Improved treatment efficiency.
7. More
rapid
control
of
the
patient's
condition.
8. Less fluctuation in drug-blood level.
9. Improved bioavailability for some drugs.
10. Improved ability to provide special effects
(e.g., morning relief of arthritis by bedtime
dosing).
11. Reduced cost.
RATE-CONTROLLED RELEASE IN DRUG
DELIVERY AND TARGETING

There are a number of mechanisms by which drug
release rate is controlled:
• Diffusion-controlled release mechanisms
• Dissolution-controlled release mechanisms
• Osmosis-controlled release mechanisms
• Mechanical-controlled release mechanisms
• Bio-responsive controlled release mechanisms
DRUG TARGETING SYSTEMS

Advantages of Drug targeting delivery:
o improve Drug safety, minimized toxic side-effects
caused by drug action at non-target sites .
o improve Drug efficacy, as the drug is concentrated at
the site of action rather than being dispersed
throughout the body.
o improve Patient compliance, as increased safety and
efficacy make therapy more acceptable .
STRATIGES TO ACHIVE DRUG
TARGETING SYSTEMS
 local administration of drug with conventional
dosage forms.
 Targeting the
skin by apply the drug as
ointment, lotion, or cream.
 Direct injection of an anti-inflammatory agent
into a joint.
 oral delivery, targeting the drug to the small
intestine, colon, or gut lymphatics. By using
enteric coatings, prodrugs , osmotic pumps,
colloidal carriers and hydrogels .

By parenteral administration.
are most advanced , delivering drug to specific
targets sites , protect drugs from degradation &
premature elimination.
include the use of carriers as :



Soluble carriers ; as monoclonal antibodies,
dextrans , soluble synthetic polymers.
Particulate carriers, such as liposomes, microand nano- particles, microspheres.
Target-specific recognition moieties, such as
monoclonal antibodies, carbohydrates & lectins
.
Pharmaceutical carriers
DOSAGE FORMS FOR ADVANCED DRUG
DELIVERY AND TARGETING

Are
available,
range
in
of
sizes,
molecular
level
devices.
a
from
to
wide
the
large
Molecular




Drugs attached to water-soluble carriers, such as
monoclonal antibodies, carbohydrates, lectins and
immuno-toxins.
Such systems achieve site-specific drug delivery
following parenteral administration.
Release of the attached drug molecules at the
target site achieved by enzymatic or hydrolytic
cleavage.
Larger complexes include drug conjugates with
soluble natural or synthetic polymers.
Nano- and Micro-particles

Nanoparticles
are
solid
colloidal
particles,
generally less than 200 nm.

Such systems include us of drug carrier polymer
poly (alkyl- cyanoacrylate)

Nanoparticles used for parenteral drug targeting
delivery.

Liposomes , vesicular structures based on one
or more lipid bilayer(s) encapsulating an
aqueous
carriers.
core
represent
highly
versatile

Microparticles are colloidal particles in the, in
the size range 0.2-100 µm.

Include use of Synthetic polymers, such as
poly (lactide-co-glycolide) as drug carrier.

Include use of Natural polymers, such as
albumin, gelatin , starch, used as microparticulate drug carriers.
Macrodevices
are widely used in many applications, including:

Parenteral drug delivery: mechanical pumps,
implantable devices.

Oral drug delivery: solid dosage forms such as
tablets
and
capsules
which
incorporate
controlled release/ targeting technologies.

Buccal drug delivery: buccal adhesive patches
and films.





Transdermal
drug
delivery:
patches, iontophoretic devices.
Nasal drug delivery:
transdermal
nasal sprays and drops.
Pulmonary
drug
delivery:
metered-dose
inhalers, dry-powder inhalers, nebulizers.
Vaginal drug delivery: vaginal rings, creams,
sponges.
Ophthalmic drug delivery: ophthalmic drops
and sprays.
Properties of an "ideal"
Drug Delivery dosage form
1. Good Patient acceptability and compliance


Parenteral delivery This is painful for the
patient, and requiring the intervention of
medical professionals.
The oral route, involves swallowing a tablet,
liquid or capsule, thus a much more convenient
and attractive route for drug delivery.

Transdermal patches are also well accepted by
patients and convenient.

Nebulizers, pessaries and suppositories, have
more limited patient compliance.
2) Reproducibility

The dosage form should allow accurate and
reproducible drug delivery, particularly for drugs
with a narrow therapeutic index.
3) Ease of termination



The dosage form should be easily removed either
at the end of an application period, or in the case
of toxicity.
Transdermal adhesive patches and buccal tablet
are easily removed
Non-biodegradable
polymeric
implants
and
osmotic pumps must be surgically take back at
the end of treatment.
4)Biocompatibility and absence of adverse effects

The drug delivery system should be non-toxic and
non-immunogenic .

Dosage forms containing penetration enhancers
has a harmful effects on epithelial tissue as well as
the increased epithelial permeability may allow the
entrance of potentially toxic agents.
5) Large effective area of contact

For drugs absorbed via passive mechanisms,
increasing the area of contact of the drug with
the absorbing surface will increase the amount
absorbed.

The dosage form can influence the size of the
area over which the drug is absorped . For
example, increasing the size of a transdermal
patch increases transdermal bioavailability.
6) Prolonged contact time



Ideally, the dosage form should facilitate a
prolonged contact time between the drug and the
absorbing surface, thereby facilitating absorption.
Drug delivery to epithelial sites is often limited by
a variety of physiological clearance mechanisms
at the site of administration as mucociliary
clearance and intestinal motility.
Bioadhesive materials (sometimes also termed
mucocadhesive) adhere to biological substrates
such as mucus or tissue and increase the
effective contact time.
Properties of an "ideal" route of
administration

maximize the amount of drug entering the systemic
circulation from the site of administration, the
delivery site should possess certain properties:
1. A large surface area
2. Low metabolic activity
3. Long Contact time
4. Adequate blood flow
5. Accessibility
6. Lack of variability
7. Permeability
1) Large surface area

A large surface area are facilitates absorption.

Due to the presence of the villi and the microvilli,
the available surface area of the small intestine of
the gastrointestinal tract is very large, which is
important for oral drug delivery.

The surface area of the lungs is broad making this
region
a
parenteral
delivery.
promising
alternative
route
and
routes
systemic
oral
for
to
the
drug
2) Low metabolic activity

Degradative enzymes may deactivate the drug, prior
to absorption.

Poor drug bioavailability may thus be expected from
an absorption site in which enzyme activity is high,
such as the gastrointestinal tract. Furthermore,
drugs which are orally absorbed must first pass
through the intestinal wall and the liver, prior to
reaching the systemic circulation. These" first-pass"
effects can result in a significant loss of drug
activity.

Drug delivery via other routes (nasal, buccal etc.)
avoid intestinal
first-pass
effects,
as
metabolic
activity at these sites is often lower than in the
gastrointestinal
tract,
these
routes
are
highly
attractive alternatives for the systemic delivery of
enzymatically labile drugs.
3) Contact time

The length of time the drug is in contact with
the absorbing tissue will influence the amount
of drug which crosses the mucosa.

Materials administered to different sites of the
body
are
removed
administration
by
a
clearance mechanisms.
from
the
variety
of
site
of
natural

For example, intestinal motility moves material in the
stomach
or
small
intestine
towards
the
large
intestine.

In the buccal cavity, the administered dosage form is
washed daily with 0.5-2 liters of saliva.

In the nasal cavity and the upper and central lungs,
an efficient selfcleansing mechanism referred to as
the "mucociliary escalator" is in place to remove any
foreign material.

In the eye, materials are diluted by tears and
removed via the lachrymal drainage system.
4) Blood supply

Adequate blood flow from the absorption
site is required to carry the drug to the site
of action post-absorption.
5) Accessibility

Certain absorption sites, for example the alveolar
region of the lungs, are not readily accessible and
thus may require quite complex delivery devices
to ensure the drug reaches the absorption site.

Delivery
efficiency
to
such
sites
may
also
therefore be low.
In contrast, other sites, such as the skin, are
highly accessible.
6) Lack of variability

Lack
of
variability
is
essential
to
ensure
reproducible drug delivery.

This is important principle for the delivery of
highly potent drugs with a narrow therapeutic
window.

Due to such factors as extremes of pH, enzyme
activity, intestinal motility, presence of food/
fluid etc., the gastrointestinal tract can be a
highly variable absorption site.

Diseases such as the common cold and hay fever
are alter the physiological conditions of the nose,
contributing to the variability of this site.

The presence of disease can also compromise the
reproducibility of drug delivery in the lungs.

Cyclic changes in the female menstrual cycle mean
that large fluctuations in vaginal bioavailability.
7) Permeability

A more permeable epithelium obviously facilitates
greater absorption.

Some epithelia are relatively more permeable than
others.

For example, the skin is an extremely impermeable
barrier,
whereas
the
permeability
of
the
lung
membranes towards many compounds is much
higher than the skin and is also higher than that of
the small intestine and other mucosal routes.

The vaginal epithelium is relatively permeable,
particularly at certain stages of the menstrual cycle.
STRATEGIES TO INCREASE DRUG
ABSORPTION
a) Manipulation of the Drug

The physicochemical properties of a drug
which influence drug absorption include:
• lipid solubility and partition coefficient.
• pKa.
• molecular weight and volume.
• aqueous solubility.
• chemical stability.

These properties can be manipulated to achieve
more favorable absorption characteristics for a
drug
 For example, various lipidization strategies can be
employed to increase the lipophilicity of the drug
and
thereby
ability
and
increase
absorption
its
via
membrane-penetrating
transcellular
passive
diffusion.
 The hydrogen-bonding tendency of a drug molecule
can be minimized by substitution, esterification or
alkylation of existing groups on the molecules,
which will decrease the drug's aqueous solubility
and favoring partitioning of the drug into lipidic
membranes.

Drug solubility may be enhanced by the use of
amorphous or anhydrous forms, or the use of the
corresponding salt form of a lipophilic drug.

Low molecular weight analogues of an active moiety
can
be
developed,
transport.
By
to
prepare
facilitate
trans-membrane
derivatives
which
are
substrates of natural transport carriers like peptides.
b) Manipulation of the formulation

Various
formulation
additives
may
be
included in the dosage form in order to
maximize drug absorption.
1. Penetration enhancers

Penetration enhancers are substances that
facilitate
absorption
biological membranes.
of
solutes
across
2. Mucoadhesives


Mucoadhesives, which are generally hydrophilic
polymers, may be included in a dosage form to
increase drug bioavailability.
These agents are believed to act by:
• Increasing the contact time of the drug at the
absorbing surface.
• Increasing the local drug concentration at the
site of adhesion/absorption.
• Protecting the drug from dilution and possible
degradation.
3. Enzyme inhibitors

Enzyme inhibitors in a formulation may help
to overcome the enzymatic activity of the
epithelial barrier.

The use of protease inhibitors facilitates the
absorption
proteins.
of
therapeutic
peptides
and