DRUG DELIVERY

SYSTEMS
(SISTEM
PENGHANTARAN OBAT)

INTRODUCTION
A drug delivery system (DDS) is defined as.....
...a formulation or a device
...that enables the introduction of a therapeutic substance
in the body and
...improves its efficacy and safety
...by controlling the rate, time, and place of release of drugs
in the body.
This process includes:
1 - the administration of the therapeutic product,
2 - the release of the active ingredients by the product, and
3 - the subsequent transport of the active ingredients across
the biological membranes to the site of action.

INTRODUCTION
The term therapeutic substance also applies to
an agent such as gene therapy that will induce in
vivo production of the active therapeutic agent.
Gene therapy can fit in the basic and broad
definition of a drug delivery system.
Gene vectors may need to be introduced into the
human body by novel delivery methods.
However, gene therapy has its own special
regulatory control.

INTRODUCTION
Drug delivery system is an interface between the patient and the
drug.
It may be.....
a formulation of the drug to administer it for a therapeutic purpose or
a device used to deliver the drug.
This distinction between the drug and the device is important, as it is
the criterion for regulatory control of the delivery system by the drug
or medicine control agency.

INTRODUCTION
If a device is introduced into the human body
for purposes other than drug administration,
such as therapeutic effect by a physical
modality or a drug may be incorporated into the
device for preventing complications resulting from the
device,
it is regulated strictly as a device.
There is a wide spectrum between drugs and
devices, and the allocation to one or the other
category is decided on a case by case basis.

Drug Delivery Routes

Drugs may be introduced into the human body by
various anatomical routes.
They may be intended for systemic effects or
targeted to various organs and diseases.
The choice of the route of administration
depends on:
(1) the disease,
(2) the effect desired, and
(3) the product available.

Drug Delivery Routes

Drugs may be introduced into the human body by
various anatomical routes.
Drugs may be:
(1) administered directly to the organ affected
by disease or
(2) given systemically and targeted to the
diseased organ.

A classification of various
anatomical routes
for systemic drug delivery
1. Gastrointestinal
system
Oral
Rectal

3. Transmucosal:
buccal
mucosa lining the rest
of gastrointestinal tract
4. Transnasal
2. Parenteral
5. Pulmonary
Subcutaneous injection drug delivery by
Intramuscular injection
inhalation
Intravenous injection
6. Transdermal drug
Intra-arterial injection
delivery

A classification of various
anatomical routes
for systemic drug delivery
Comparison of major routes of
drug delivery for systemic absorption

Drug Formulations
There is constant evolution of the
methods of delivery, which involves
modifications of conventional
methods and discovery of new
devices.
A classification of technologies that
affect the release and availability of
drugs is shown in the Table.

Classification of DDS that affect

the release and availability
of drugs

Systemic versus localized drug delivery

General non-targeted delivery to all tissues
Targeted delivery to a system or organ
Controlled release delivery systems (systemic delivery)
Release on timescale
Immediate release
Programmed release at a defined time/pulsatile release
Delayed, sustained, or prolonged release, long acting
Targeted release (see also drug delivery devices)
Site-specific controlled release following delivery to a target
organ
Release in response to requirements or feedback
Receptor-mediated targeted drug delivery
Type of drug delivery device

Novel preparations for improving

bioavailability of drugs

Oral drug delivery

Fast-dissolving tablets
Technologies to increase gastrointestinal retention time
Technologies to improve drug release mechanisms of oral
preparations
Adjuvants to enhance absorption
Methods of increasing bioavailability of drugs
Penetration enhancement
Improved dissolution rate
Inhibition of degradation prior to reaching site of action
Production of therapeutic substances inside the body
Gene therapy
Cell therapy

Novel carriers for drug delivery

Polymeric carriers for drug delivery
Collagen
Particulate drug delivery systems:
microspheres
Nanobiotechnology-based methods, including
nanoparticles such as liposomes
Glass-like sugar matrices
Resealed red blood cells
Antibody-targeted systems

Biodegradable implants for

controlled sustained drug delivery
Injectable implants
Gels
Microspheres
Surgical implants
Sheets/films
Foams
Scaffolds

Ideal Properties of Material

for Drug Delivery
1. Structural control over size and shape of drug or
imaging-agent cargo-space.
2. Biocompatible, nontoxic polymer/pendant functionality.
3. Precise, nano scale-container and/or scaffolding
properties with high drug or imaging-agent capacity
features.
4. Well-defined scaffolding and/or surface modifiable
functionality for cell specific targeting moieties.
5. Lack of immunogenicity.
6. Appropriate cellular adhesion, endocytosis, and
intracellular trafficking to allow therapeutic delivery or
imaging in the cytoplasm or nucleus.

Ideal Properties of Material

for Drug Delivery
7. Acceptable bioelimination or biodegradation.
8. Controlled or triggerable drug release.
9. Molecular level isolation and protection of the
drug against inactivation during transit to target
cells.
10.Minimal nonspecific cellular and blood-protein
binding properties.
11.Ease of consistent, reproducible, clinical-grade
synthesis.

Classification of
drug delivery devices

Surgically implanted devices for prolonged sustained drug

release
Drug reservoirs
Surgically implanted devices for controlled/intermittent drug
delivery
Pumps and conduits
Implants for controlled release of drugs (non-biodegradable)
Implantable biosensor-drug delivery system
Microfluidics device for drug delivery
Controlled-release microchip
Implants that could benefit from local drug release
Vascular stents: coronary, carotid, and peripheral vascular
Ocular implants
Dental implants
Orthopedic implants

New Concepts in Pharmacology

That Influence Design of DDS
Pharmacology, particularly pharmacokinetics and
pharmacodynamics, have traditionally influenced drug
delivery formulations.
Some of the newer developments in pharmacology and
therapeutics that influence the development of DDSs are
as follows:
1. Pharmacogenetics
2. Pharmacogenomics
3. Pharmacoproteomics
4. Pharmacometabolomics
5. Chronopharmacology
The first four items are linked together and form the basis
of personalized medicine.

Current trends in
pharmaceutical product
development

Use of recombinant DNA technology

Expansion of use of protein and peptide drugs in current
therapeutics
Introduction of antisense, RNA interference, and gene therapy
Advances in cell therapy: introduction of stem cells
Miniaturization of drug delivery: microparticles and nanoparticles
Increasing use of bioinformatics and computer drug design
A trend toward development of target-organ-oriented dosage
forms
Increasing emphasis on controlled-release drug delivery
Use of routes of administration other than injections
Increasing alliances between pharmaceutical companies and DDS
companies

Aims of DDS
Development
Drug delivery technologies are aimed at improving
efficacy and safety of medicines as well as
commercial pharmaceutical development.

The following are the important points:

Improvement of drug safety and efficacy
Improved compliance
Chronopharmacological benefits
Reduction of cost of drug development
Life extension of the products
Reduction of risk of failure in new product
development

Characteristics of
an ideal drug delivery system
1. It should increase the bioavailability of the drug.
2. It should provide for controlled drug delivery.
3. It should transport the drug intact to the site of action
while avoiding the non-diseased host tissues.
4. The product should be stable and delivery should be
maintained under various physiological variables.
5. A high degree of drug dispersion.
6. The same method should be applicable to a wide range
of drugs.
7. It should be easy to administer to the patients.
8. It should be safe and reliable.
9. It should be cost-effective.

Integration of
Diagnostics, Therapeutics, and
Combination of diagnostics DDS
with therapeutics is an important

component of personalized medicine.

A DDS can be integrated into this combination to control the
delivery of therapeutics in response to variations in the patients
condition as monitored by diagnostics.
Nano-biotechnology has helped in this integration.
One example is use of quantum dots in cancer, where diagnosis,
therapeutics, and drug delivery can be combined using quantum
dots (QDs) as the common denominator.
The pharmaceutical industry is taking an active part in the
integration of diagnostics and therapeutics.
During drug development, there is an opportunity to guide the
selection, dosage, route of administration, and multidrug
combinations to increase the efficacy and reduce toxicity of
pharmaceutical products.

Current Achievements,
Challenges and Future of Drug
Delivery

Considerable advances have occurred in DDS within

the past decade.
Extended release, controlled release, and once-a-day
medications are available for several commonly used
drugs.
Global vaccine programs are close to becoming a
reality with the use of oral, transmucosal,
transcutaneous, and needle-less vaccination.
Considerable advances have been made in gene
therapy and delivery of protein therapeutics.
Many improvements in cancer treatment can be
attributed to novel drug delivery technologies.

Current Achievements,
Challenges and Future of Drug
Delivery

New drug delivery systems will develop during the next

decade by interdisciplinary collaboration of material
scientists, engineers, biologists, and pharmaceutical
scientists.
Progress in microelectronics and nanotechnology is
revolutionalizing drug delivery.
However, DDS industry is still facing challenges
and some of these are as follows:
1. Drug delivery technologies require constant
redesigning
to keep up with new methods of drug
design and
manufacture, particularly of
biotechnology products.

Current Achievements,
Challenges and Future of Drug
Delivery

However, DDS industry is still facing

challenges and some of these are as follows:
2. As the costs of drugs are rising, drug delivery
aims to reduce the costs by improving the
bioavailability of drugs
so that lesser quantities
need to be taken in by the patient.
3. More fundamental research needs to be done to
characterize the physiological barriers to therapy
such as the blood-brain barrier.
4. New materials that are being discovered, such as
nanoparticles, need to have safety studies and
regulatory
approval.

Reference
Jain KK, ed. 2008. Drug Delivery Systems. NJ:
Humana Press.