A drug delivery system (DDS) is defined
as a formulation or a device that enables the introduction of a pharmaceutical
compound in human beings to achieve therapeutical effects and improve its
efficacy and safety by controlling the speed and the place of release of drugs
in the body. The term pharmaceutical compound 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.
Various routes of drug delivery system
Drugs can be administered into
the human body by various anatomical ways. They may be intended for systemic
effects or targeted to various organs and diseases. Drugs may be administered
directly to the organ affected by the disease or given systemically and
targeted to the diseased organ. The choice of the way of administration depends
on the effect desired, the disease and the chemical formulation of the product.
A classification of various routes of systemic drug delivery by anatomical ways
is shown in Table 1.1
Oral Drug Delivery
The oral route of drug administration has
been, generally, the most used for both traditional as well as novel drug
delivery. The reasons for this preference are obvious because of the ease of
administration and widespread acceptance by patients. However, the oral drug
delivery system has many limitations such as:
Sustained release and controlled-release
systems due to the variation of the absorption rates and the serum concentrations
which may be unpredictable.
The high level of acid in the digestive
tract can degrade some drugs well before they reach the site of absorption into
the bloodstream. This is a particular problem for ingested proteins. Therefore,
this route has limitations for administration of biotechnology products.
Many compounds cannot effectively traverse
the cells of the epithelial membrane in the small intestines to reach the
bloodstream. Their use is limited to local effect in the gastrointestinal tract
and also some drugs irritate the gastrointestinal tract and this is partially
counteracted by coating.
Many drugs become insoluble at the low pH
levels encountered in the digestive tract. Since only the soluble form of the
drug can be absorbed into the bloodstream, the transition of the drug to the
insoluble form can significantly reduce his bioavailability.
Oral route is not suitable for drugs
targeted to specific organs.
Nowadays, many researchers still trying to
make several modifications in the formulation of drugs for oral delivery for
improving their action.
Parenteral Drug Delivery
Parenteral literally means introduction of
substances into the body by injection of substances by subcutaneous,
intramuscular, intravenous, and intra-arterial routes. Injections made into
specific organs of the body for targeted drug delivery will be described under
various therapeutic areas. Parenteral administration of the drugs is the most
commonly used method of drug delivery. Many important drugs are available only
in parenteral form.
Advantages of parenteral administration
Major drawbacks of parenteral
Rapid onset of action.
Injection is not an ideal method of
delivery because of pain involved and patient compliance becomes a major
Predictable and almost complete
Injections have limitations for the
delivery of protein products, particularly those that require sustained
Avoidance of the gastrointestinal tract
with problems of oral drug administration.
Provides a reliable route for drug
administration in very ill and comatose patients, who are not able to ingest
Transdermal Drug Delivery
Transdermal drug delivery is an approach
used to deliver drugs through the skin for therapeutic use as an alternative to
oral, parenteral routes. It includes the following categories of drug
Local application formulations (
Drug carriers (liposomes and nanoparticles)
Transdermal patches and transdermal
Use of physical modalities to facilitate
transdermal drug transport
detailed description of technologies and commercial aspects of development are
described in a special report on this topic 1.
Transmucosal Drug Delivery
Mucous membrane covers all the internal orifices
of the body such as buccal, nasal, rectal, and drugs can be introduced at
various anatomical sites. Movement of penetrants across the mucous membranes is
by diffusion. As in the epidermis of the skin, the pathways of permeation
through the epithelial barriers are intercellular rather than intracellular. Delivery
of biopharmaceuticals across mucosal surfaces may offer several advantages over
injection techniques, which include the following:
1. Avoidance of an injection
2. Increase of therapeutic efficiency
3. Possibility of administering peptides
4. Rapid absorption when compared with oral
5. Bypassing first pass metabolism by the
6. Higher patient acceptance when compared
The ideal vehicle is the one in which the
drug is minimally soluble.
attractive features of buccal drug administration
Limitations to the use of buccal route
Quick absorption into the systemic circulation
The tablet must be kept in place and not
chewed or swallowed.
The tablet can be removed in case of an
Excessive salivary flow may cause a very
rapid dissolution and absorption of the tablet or wash it away.
Oral mucosal absorption avoids the first
pass hepatic metabolism.
A bad-tasting tablet will have a low
A tablet can remain for a prolonged
period in the buccal cavity, which enables development of formulations with
Some of these disadvantages have been
overcome by the use of a patch containing the drug that is applied to the
buccal mucosa or by using the drug as a spray.
This route can be used in patients with
The tablet must be kept in place and not
chewed or swallowed.
Nasal Drug Delivery
Drugs have been administered nasally for
several years both for topical and systemic effect. Topical administration
includes agents for the treatment of nasal congestion, rhinitis, sinusitis, and
related allergic and other chronic conditions. Various medications include
corticosteroids, antihistaminics, anticholinergics, and vasoconstrictors. The focus
in recent years has been on the use of nasal route for systemic drug delivery.
Intranasal drug delivery. Intranasal route is considered for drugs
that are ineffective orally, are used chronically, require small doses, and
where rapid entry into the circulation is desired. The rate of diffusion of the
compounds through the nasal mucous membranes, like other biological membranes,
is influenced by the physicochemical properties of the compound. However, in
vivo nasal absorption of compounds of molecular weight less than 300 is not significantly
influenced by the physicochemical properties of the drug. Factors such as the
size of the molecule and the ability of the compound to hydrogen bond with the
component of the membrane are more important than lipophilicity and ionization
state. The absorption of drugs from the nasal mucosa most probably takes place
via the aqueous channels of the membrane. Therefore, as long as the drug is in solution
and the molecular size is small, the drug will be absorbed rapidly via the
aqueous path of the membrane. The absorption from the nasal cavity decreases as
the molecular size increases.
Nasal drug absorption can be accomplished
by use of prodrugs, chemical modification of the parent molecule, and use of
physical methods of increasing permeability. Special excipient used in the
nasal preparations comes into contact with the nasal mucosa and may exert some
effect to facilitate the drug transport. The mucosal pores are easier to open
than those in the epidermis.
Alternative means that help overcome these
nasal barriers are currently in development. Absorption enhancers such as
phospholipids and surfactants are constantly used, but care
Advantages of nasal drug delivery
Disadvantages of nasal drug delivery
High permeability of the nasal mucosa,
compared with the epidermis or the gastrointestinal mucosa
Diseases conditions of the nose may
result in impaired absorption.
Highly vascularized subepithelial tissue
Dose is limited because of relatively
small area available for absorption.
Rapid absorption, usually within half an
Time available for absorption is limited.
Avoidance of first pass effect that
occurs after absorption of drugs from the gastrointestinal tract
Little is known of the effect of common
cold on transnasal drug delivery, and it is likely that instilling a drug
into a blocked nose or a nose with surplus of watery rhinorrhea may expel the
medication from the nose.
Avoidance of the effects of gastric
stasis and vomiting, for example, in migraine patients
The nasal route of delivery is not
applicable to all drugs. Polar drugs and some macromolecules are not absorbed
in sufficient concentration because of poor membrane permeability, rapid
clearance, and enzymatic degradation into the nasal cavity.
Ease of administration by the patients,
who are usually familiar with nasal drops and sprays
Higher bioavailability of the drugs than
in the case of gastrointestinal route or pulmonary route
Drug delivery systems, including liposomes,
cyclodextrins, and micro- and nanoparticles are being investigated to increase
the bioavailability of drugs delivered intranasally 2.
After a consideration of advantages as well
as disadvantages, nasal drug delivery turns out to be a promising route of
delivery and competes with pulmonary drug, which is also showing great
potential. One of the important points is the almost complete bioavailability
and precision of dosage.
Colorectal Drug Delivery
Although drug administration to the rectum
in human beings dates back to 1,500 B.C., majority of pharmaceutical consumers
are reluctant to administer drugs directly by this route. However, the colon is
a suitable site for the safe and slow absorption of drugs which are targeted at
the large intestine or designed to act systematically. Although the colon has a
lower absorption capacity than the small intestine, ingested materials remain
in the colon for a much longer time. Food passes through the small intestine
within a few hours but it remains in the colon for 2–3 days. Basic requirements
of drug delivery to the colorectal area are as follows:
1. The drug should be delivered to the
colon either in a slow release or targeted form ingested orally or introduced
directly by an enema or rectal suppository.
2. The drug must overcome the physical
barrier of the colonic mucous.
3. Drugs must survive metabolic
transformation by numerous bacterial species resident in the colon, which are
mainly anaerobes and possess a wide range of enzymatic activities.
Drugs administered by rectal route. Advantages of the rectal route for drug
administration are as follows:
1. A relatively large amount of the drug
can be administered.
2. Oral delivery of drugs that are
destroyed by the stomach acid and/or metabolized by pancreatic enzymes.
3. This route is safe and convenient
particularly for the infants and the elderly.
4. This route is useful in the treatment of
emergencies such as seizures in infants when the intravenous route is not
5. The rate of drug absorption from the
rectum is not influenced by ingestion of food or rate of gastric emptying.
6. The effect of various adjuvants is
generally more effective in the rectum than in the upper part of the
7. Drugs absorbed from the lower part of
the rectum bypass the liver.
8. Degradation of the drugs is much less in
the rectal lumen than in the upper gastrointestinal tract.
Disadvantages of the rectal route for drug
administration are as follows:
1. Some hydrophilic drugs such as
antibiotics and peptide drugs are not easily absorbed from the rectum and
absorption enhancers are required.
2. Drugs may cause rectal irritation and
sometimes proctitis with ulceration and bleeding. Drugs targeted for action in
the colon can also be administered orally. Oral drug delivery to the colon has
attracted significant attention during the past 20 years. Colon targeting is
recognized to have several therapeutic advantages, such as the oral delivery of
drugs that are destroyed by the stomach acid and/or metabolized by pancreatic
enzymes. Sustained colonic release of drugs can be useful in the treatment of
nocturnal asthma, angina, and arthritis. Local treatment of colonic pathologies,
such as ulcerative colitis, colorectal cancer, and Crohn’s disease, is more
effective with the delivery of drugs to the affected area 3. Likewise, colonic
delivery of vermicides and colonic diagnostic agents requires smaller doses.
Pulmonary Drug Delivery
Although aerosols of various forms for
treatment of respiratory disorders have been in use since the middle of the
twentieth century, the interest in the use of pulmonary route for systemic drug
delivery is recent. Interest in this approach has been further stimulated by
the demonstration of potential utility of lung as a portal for entry of peptides
and the feasibility of gene therapy for cystic fibrosis. It is important to understand
the mechanism of macromolecule absorption by the lungs for an effective use of
Large surface area available for
absorption. ? Close proximity to blood fl ow. ? Avoidance of fi rst-pass
hepatic metabolism. ? Smaller doses are required than by the oral route to
achieve equivalent therapeutic effects. ? The lungs have an effi cient
aerodynamic fi lter which must be overcome for effective drug deposition to
occur. ? The mucous lining the pulmonary airways clears the deposited particles
toward the throat. ? Only 10–40 % of the drug leaving an inhalation device is
usually deposited in the lungs by using conventional devices.