Introduction in vivo production of the active therapeutic


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.

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Drug can be delivered through many ways
e.g. through mouth, skin (topical), nasal (transmucosal), and inhalation routes
etc. It may include a target area in the body concerned with quantity and
duration of drug presence. The objective of effective drug delivery is
improving the pharmacokinetics and pharmacodynamics of each therapeutic to
enable drug delivery to the right place, at the right time and in the right

As rate and amount of dose in the body must be carefully calculated so
in the traditional drug delivery methods where dose rate is calculated and
delivered manually any type of mishandling can lead to certain complications in
a patient. 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. 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.














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.


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 administration

Rapid onset of action.

Injection is not an ideal method of delivery because of pain involved
and patient compliance becomes a major problem.

Predictable and almost complete bioavailability.

Injections have limitations for the delivery of protein products,
particularly those that require sustained levels.

Avoidance of the gastrointestinal tract with problems of oral drug


Provides a reliable route for drug administration in very ill and
comatose patients, who are not able to ingest anything orally.



 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 administration:

Local application formulations (
transdermal gels)

Drug carriers (liposomes and nanoparticles)

Transdermal patches and transdermal

Use of physical modalities to facilitate
transdermal drug transport

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
with injectables


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 undesirable effect.

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 patient acceptability.

A tablet can remain for a prolonged period in the buccal cavity, which
enables development of formulations with sustained-release effect.

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 swallowing difficulties.

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

Rapid absorption, usually within half an hour

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

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 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
this route.