International Journal of Medical and Pharmaceutical Sciences

PRODRUG APPROACH: AN EFFECTIVE SOLUTION

TO OVERCOME SIDE-EFFECTS

Patil S.J., P.J. Shirote

IJMPS Department of Pharmaceutical Chemistry, Appasaheb Birnale College of
Vol 01 issue 07 Pharmacy, Sangli
Category: Review
Received on: 05/08/11
Revised on: 15/09/11 Corresponding author E-mail: smtz123@rediffmail.com
Accepted on: 03/10/11

ABSTRACT
Prodrug design is a choice of approach in solving many of the stability, solubility, permeability and
targeting problems that plague drug discovery and development. The prodrug approach has the ability to
keep promising new drug candidates alive through development, and improving the safety and efficacy of
existing drug products. It is a very fruitful area of research and its introduction in human therapy has
given successful results in improving the clinical and therapeutic effectiveness of drugs suffering from
undesirable side-effects. About 14% of drugs approved worldwide can be classified as prodrugs. The
present article takes a review of introduction and applications of prodrug design in various areas of drug
development by overcoming side-effects of existing drugs.
______________________________________________________________________________

Keywords Prodrug, Carrier, Pro-moiety,
Parent drug, Bioprecursor, Mutual prodrug,
INTRODUCTION
Almost all drugs possess some undesirable
physicochemical and biological properties. Their
therapeutic efficacy can be improved by
eliminating the undesirable properties while
retaining the desirable ones1, 2. This can be
achieved through biological, physical or
chemical means.
The biological approach is to alter the route
of administration which may or may not be
acceptable to patient.
The physical approach is to modify the
design of dosage form such as controlled
drug delivery of drug.
The third and the best approach in
enhancing drug selectivity while
minimizing toxicity, is the chemical
approach for design of prodrugs.
Prodrug design is opening new doors in the
challenging field of drug discovery,
revolutioning the art of Drug development.
Today, drug candidates are often discontinued
due to issues of poor pharmacokinetic properties
or high toxicities3. Prodrugs have the potential to
overcome these challenges. Prodrugs,
bioreversible derivatives of the original
compound, overcome physicochemical and
biological barriers to drug delivery, and convert
in vivo to the active form of the drug. The
approach exploits endogenous enzymes for
selective bioconversion of the prodrug to the
active form of the drug. This approach has the
ability to keep promising new drug candidates
alive through development, and improving the
safety and efficacy of existing drug products4.
Prodrugs have become an established concept
and a powerful tool in optimizing the
pharmacologically potent structures and
overcoming physicochemical, pharmaceutical

International Journal of Medical and Pharmaceutical Sciences (IJMPS) Vol 1 issue 7 www.ijmps.com Page 1
and biopharmaceutical barriers to a drug's
usefulness5. A prodrug is a chemically modified
inert drug precursor, which upon
biotransformation liberates the
pharmacologically active parent compound.
Chemical modification of a drug via the
attachment of pro-moiety generates the prodrug.
The properties of the prodrug enable it to cross
the limiting barrier and it is designed ideally to
be cleaved efficiently by enzymatic or non-
enzymatic processes. This is followed by rapid
elimination of the released pro-moiety6.
Prodrug design can be highly effective for
solving many of the stability, solubility,
permeability and targeting problems in drug
discovery and development. In addition to
improving oral bioavailability, prodrugs are
increasingly used for targeting purposes
including site-specific activation and delivery of
anticancer drugs to tumor tissues through
transporters, tumor- or tissue-specific enzymes,
and gene therapy. The patent literature shows a
dramatic increase in numbers of prodrug patents
(> 20% increase in 2002 compared to 1993),
with claims for cancer treatment comprising
37% of these. This increase is largely due to the
rise from North American-based multinationals
and some smaller drug delivery companies
mirroring the overall trend. In 2001 and 2002,
14% of all new approved chemical drugs were
prodrugs. It appears that prodrugs to overcome
barriers to the delivery of problematic drug
candidates are becoming an integral part of the
drug discovery paradigm7.
Prodrug concept:
The prodrug approach to drug design is a
versatile, powerful method that can be applied to
a wide range of drug administration routes and
formulations for many types of parent drug
molecule. However, for prodrug strategies to be
successful, analysis of parent-drug properties
and the proper identification of barriers are
crucial. Clinically, the majority of prodrugs are
used with the aim of enhancing drug permeation
International Journal of Medical and Pharmaceutical Sciences (IJMPS) Vol 1 issue 7 www.ijmps.com
by increasing lipophilicity and more recently by
improving water solubility. However, there are
significant needs that have not yet been
adequately addressed by prodrugs. It is
surprising how few marketed prodrug examples
exist for cancer therapy, such as those designed
to increase site-selective drug delivery, despite
the prominent side effects of anticancer agents.
In addition prevention of pre-systemic drug
metabolism and the circumvention of efflux-
limited drug absorption and distribution have not
received enough attention in prodrug research,
despite great possibilities.
The concept of prodrug was first introduced
by Adrian Albert in 1958 to describe compounds
that undergo biotransformation prior to eliciting
their pharmacological effect8. i.e. "therapeutic
agents that are inactive but can be transformed
into one or more active metabolites."
The development of prodrugs is now well
established as a strategy to improve the
physicochemical, biopharmaceutical or
pharmacokinetic properties of
pharmacologically potent compounds, and
thereby increase the developability and
usefulness of a potential drug. For example,
prodrugs provide possibilities to overcome
various barriers to drug formulation and delivery
such as poor aqueous solubility, chemical
instability, insufficient oral absorption, rapid
pre-systemic metabolism, inadequate brain
penetration, toxicity and local irritation9.
Prodrugs can also improve drug targeting, and
the development of a prodrug of an existing drug
with improved properties may represent a life-
cycle management opportunity.
In recent years numerous prodrugs have been
designed and developed to overcome barriers to
drug utilization such as10, 11.
Low oral absorption properties
Lack of site specificity
Chemical instability
Toxicity
Bad taste
Page 2
 Bad odor
A prodrug can be illustrated as shown in figure.

DRUG DRUG PROMOIETY

BARRIER

PROMOIETY DRUG
PROMOIETY DRUG

Figure 1: Fate of Prodrug

Classification of Prodrugs12: eliminate undesirable properties in the parent

A) Carrier linked prodrug:
It contains a group that can be easily removed
enzymatically (such as ester) to reveal the true
drugs. Ideally the group removed is
pharmacologically inactive and nontoxic while
the connecting bond must be labile for efficient
activation in vivo.
Carrier linked prodrug consists of the attachment
of a carrier group to the active drug to alter its
physicochemical properties. The subsequent
enzymatic or non-enzymatic mechanism releases
the active drug moiety. Hence, the carrier linked
prodrugs have a major drawback that they are
linked through covalent linkage with specialized
nontoxic protective groups or carriers or
promoieties in a transient manner to alter or
molecule.
Depending upon the nature of carrier, the carrier
linked prodrug may further be classified. It can
be further subdivided into-
1. Bipartate prodrug-
It is composed of one carrier (group) attached to
the drugs. As shown in figure, carrier linked
prodrug consists of the active drug covalently
linked to an inert carrier or transport moiety,
generally ester or amide. Such prodrugs have
greatly modified lipophilicity due to the attached
carrier. The active drug is released by hydrolytic
cleavage either chemically or enzymatically.
The Prodrug and carrier released after in vivo
enzymatical or non-enzymatical attack must be
nontoxic.

International Journal of Medical and Pharmaceutical Sciences (IJMPS) Vol 1 issue 7 www.ijmps.com Page 3
 e.g. Tolmetin-glycine prodrug
O CH3
N
CH 2CONHCH 2COOH

H3C

2. Tripartat prodrug-The carrier group is attached via linker to drug.

3. Mutual Prodrugs- is a synergistic drug with the drug to

A mutual prodrug consists of two
pharmacologically active agents coupled
together so that each acts as a
promoiety for the other agent and vice
versa. A mutual prodrug is a bipartate
or tripartate prodrug in which the carrier
which it is linked.
Benorylate is a mutual prodrug of
NSAIDs aspirin and paracetamol.
Another example is sultamicillin, which
on hydrolysis by an esterase produces
ampicillin, penicillanic acid sulfone and
formaldehyde.

B) Bioprecursors:
Bio- precursor prodrugs produce their effects after in vivo chemical modification of their
inactive form.

International Journal of Medical and Pharmaceutical Sciences (IJMPS) Vol 1 issue 7 www.ijmps.com Page 4
 Figure 2: Examples of Bioprecursor Prodrug
Bioprecursor prodrugs rely on oxidative or
reductive activation reactions unlike the
hydrolytic activation of carrier-linked prodrugs.
They metabolized into a new compound that
may itself be active or further metabolized to an
active metabolite (e.g. amine to aldehyde to
carboxylic acid).
Prerequisites of Ideal Prodrug13:
An ideal prodrug should possess following
properties
a. Pharmacological inertness.
b. Rapid transformation, chemically or
enzymatically, into the active form at the
target site.
c. Non-toxic metabolic fragments followed by
their rapid elimination.
Objectives of Prodrug design14:
Prodrug design is really not different from the
general drug discovery process, in which a
International Journal of Medical and Pharmaceutical Sciences (IJMPS) Vol 1 issue 7 www.ijmps.com
unique substance is observed to have desirable
pharmacological effects, and studies of its
properties lead to the design of better drugs.
The main objectives of a prodrug designing are:
To bring active drugs to their respective
active sites.
To provide the desired pharmacological
effects while minimizing adverse metabolic
and/or toxicological events.
To improve the clinical and therapeutic
effectiveness of those drugs which suffer
from some undesirable properties that
otherwise hinder their clinical usefulness.
To avoid the practice of clinically co-
administering two drugs in order to enhance
pharmacological activity or prevent clinical
side effects. Simultaneous administration
does not guarantee equivalent absorption or
transportation to site of action. So, mutual
prodrug concept is useful when two
Page 5
 synergistic drugs need to be administered at
the same site at the same time. Mutual
prodrugs are synthesized toward a
pharmacological objective of improving
each drug's efficacy, optimizing delivery,
and lowering toxicities.
Strengths- advantages of making Prodrug15:
1. Help in reduction of Side-effects of Parent
Drugs
2. Produces synergistic effect
3. Give additional biological action as that of
parent drug.
4. Reduction in dose due to synergistic effect
5. Improve pharmacokinetics of Parent drug
Weaknesses- Limitations of prodrug design16:
Even if prodrug design has proven highly
beneficial in overcoming various undesirable
properties of drugs, it can also give rise to a
large number of newer difficulties, especially in
the assessment of pharmacological,
pharmacokinetic, toxicological and clinical
properties.
i. Problems at the pharmacological level:
These compounds cannot be submitted to
preliminary in vitro screening tests like
binding studies, reuptake of neurotransmitter
and enzyme inhibition measurement because
bioactivation to their active species is
necessary.
ii. Problems at the toxicological level: Even
though mutual prodrugs are derived from
well-known active principles, they have to be
regarded as new entities. In a review by
Gored, he has cited certain toxicity
mechanisms like formation of toxic metabolite
of total prodrug which is not produced by the
parent drugs, consumption of vital constituent
during prodrug activation process, generation
of a toxic derivative, release of a
pharmacokinetic modifier which may cause
enzyme induction or alter drug excretion.
iii. Problems at the pharmacokinetic Studies:
The mutual prodrug may not be an ideal
substrate for the activating enzymes. So, it is
International Journal of Medical and Pharmaceutical Sciences (IJMPS) Vol 1 issue 7 www.ijmps.com
necessary to consider modifying the carrier
with electron withdrawing or donating groups
to facilitate the hydrolysis. Pharmacokinetic
studies may lead to numerous
misinterpretations. When mutual prodrug and
parent molecules are being compared, one
must take into account the differences in their
respective time courses of action. The
maximum activity may appear later for mutual
prodrug than for parent compounds, so area
under the curve should be compared as it
presents a better criterion for comparison.
iv. Problems at the clinical stage: The
predictive value of animal experiments is also
questionable. The active doses of two mutual
prodrugs of the same parent drugs may appear
to be same in rats but may be quite different in
clinical investigations.
Functional Groups Amenable to Prodrug
Design17:
Ideally, the design of an appropriate prodrug
structure should be considered at the early stages
of preclinical development, bearing in mind that
prodrugs might alter the tissue distribution,
efficacy and the toxicity of the parent drug.
Several important factors should be carefully
examined when designing a prodrug structure,
including:
Parent drug: which functional groups are
amenable to chemical prodrug derivatization.
Promoiety: this should ideally be safe and
rapidly excreted from the body. The choice of
promoiety should be considered with respect
to the disease state, dose and the duration of
therapy.
Parent and prodrug: the absorption,
distribution, metabolism, excretion (ADME)
and pharmacokinetic properties need to be
comprehensively understood.
Some of the most common functional groups
that are amenable to prodrug design include
carboxylic, hydroxyl, amine,
phosphate/phosphonate and carbonyl groups.
Prodrugs typically produced via the modification
Page 6
of these groups include esters, carbonates,
carbamates, amides, phosphates and oximes.
However, other uncommon functional groups
have also been investigated as potentially useful
structures in prodrug design. For example, thiols
react in a similar manner to alcohols and can be
derivatized to thioethers and thioesters. Amines
may be derivatized into imines and NMannich
bases.
1. Esters as prodrugs of carboxyl, hydroxyl
and thiol functionalities:
Esters are the most common prodrugs used, and
it is estimated that approximately 49% of all
marketed prodrugs are activated by enzymatic
hydrolysis. Ester prodrugs are most often used to
enhance the lipophilicity, and thus the passive
membrane permeability, of water soluble drugs
by masking charged groups such as carboxylic
acids and phosphates. The synthesis of an ester
prodrug is often straightforward. Once in the
body, the ester bond is readily hydrolysed by
ubiquitous esterases found in the blood, liver
and other organs and tissues, including carboxyl
esterases, acetylcholinesterases,
butyrylcholinesterases, paraoxonases and
arylesterases.
Figure 3. Functional groups amenable to prodrug design
International Journal of Medical and Pharmaceutical Sciences (IJMPS) Vol 1 issue 7 www.ijmps.com
2. Carbonates and carbamates as prodrugs
of carboxyl, hydroxyl or amine
functionalities:
Carbonates and carbamates differ from esters by
the presence of an oxygen or nitrogen on both
sides of the carbonyl carbon. They are often
enzymatically more stable than the
corresponding esters but are more susceptible to
hydrolysis than amides. Carbonates are
derivatives of carboxylic acids and alcohols, and
carbamates are carboxylic acid and amine
derivatives. The bioconversion of many
carbonate and carbamate prodrugs requires
esterases for the formation of the parent drug.
3. Amides as prodrugs of carboxylic acids
and amines:
Amides are derivatives of amine and carboxyl
functionalities of a molecule. In prodrug design,
amides have been used only to a limited extent
owing to their relatively high enzymatic stability
in vivo. An amide bond is usually hydrolyzed by
ubiquitous carboxylesterases, peptidases or
proteases. Amides are often designed for
enhanced oral absorption by synthesizing
substrates of specific intestinal uptake
transporters.
Page 7
4. Oximes as derivatives of ketones, amidines applied to encompassing variety of drugs;
and guanidines: various goals achieved not only for correction of
Oximes (for example, ketoximes, amidoximes pharmacokinetic behavior but also
and guanidoximes) are derivatives of ketones, pharmaceutical, organoleptic, physical and
amidines and guanidines, thus providing an chemical properties of parent drug compound
opportunity to modify molecules that lack which enhance the stability and patient
hydroxyl, amine or carboxyl functionalities. compliance improving the efficacy of therapy.
Oximes are hydrolyzed by the versatile 1. To enhance aqueous solubility:
microsomal cytochrome P450 (CYP450) Prednisolone (R=R1=H) and
enzymes, better known as xenobiotic methylprednisolone (R=CH3, R1=H) are
metabolizing enzymes. Oximes, especially poorly water soluble corticosteroid drugs. To
strongly basic amidines and guanidoximes, can permit aqueous injection or ophthalmic
be used to enhance the membrane permeability delivery of these drugs, they must be
and absorption of a parent drug. converted into water soluble forms.
Applications of prodrug approach 18-20: Prednisolone phosphate (R=H, R1=PO3Na2)
Prodrug approach has been extensively studied is prescribed as a water soluble prodrug for
amongst the drug design scientist for a wide prednisolone that is activated in vivo by
range of applications. It has been successfully phosphatases.
O
OR

R
OH
CH3

CH3
OH
O
2. Prodrugs for improved absorption pruritic skin conditions can be made more
and distribution: If the desired drug is not suitable for topical absorption by esterification
absorbed and transported to the target site in or acetonidation.For example, both fluocinolone
sufficient concentration, it can be made more acetonide (R=H) and fluocinonide (R=COCH3)
water-soluble or lipid soluble depending on the are prodrugs used for inflammatory and pruritic
desired site of action. Corticosteroids for the manifestations. Once absorbed through the skin
topical treatment of inflammatory, allergic and ,an esterase release the drug.
OCH 3
O
H OR
F H
CH3
O
CH3

CH3
OH
O F
3. Prodrugs for site specificity: The use very precise and direct effects at the "site of
of prodrugs has been actively pursued to achieve action," with minimal effect on the rest of the

International Journal of Medical and Pharmaceutical Sciences (IJMPS) Vol 1 issue 7 www.ijmps.com Page 8
body. In the prodrug approach site-specific drug
delivery can be obtained from tissue specific
activation of a prodrug, which is the result of
metabolism by an enzyme that is either unique
for the tissue or present at a higher concentration
(compared with other tissues); thus, it activates
the prodrug more efficiently. For example,
tumour cells contain a higher concentration of
phosphates and amidases than do normal cells.
Consequently a prodrug of cytotoxic agent could
be directed to tumour cells if either of these
enzymes was important to prodrug activation
process. Diethylstilbestrol diphosphate was
designedfor site-specific delivery of
diethylstilbestrol to prostatic carcinoma tissue.
OR

H3C

CH3

OR

4. Prodrugs for stability: A drug may be metabolites are propranolol O- glucuronide

rapidly metabolized and rendered inactive before (R=H, OR= glucuronide), p-
it reaches the sight of action. The structure may hydroxypropranolol (R=OH, R=H). The
be modified to block the metabolism until the hemisuccinate ester of propranolol (R=H R=,
drug is at the desired site. Some prodrugs protect COCH2COOH) was prepared to block
the drug from first-pass effect. Propranolol, glucuronide formation. Hence oral
(R=R1=H) is a widely used antihypertensive administration of propranolol hemisuccinate
drug, but because of first-pass elimination, an elevates plasma levels of propranolol for about 8
oral dose has a much lower bioavailability than times.
does intravenous injection. The major

NHCH(CH 3)2
OR'

R
5. Prodrugs for prolonged release: The Because the drug is taken less
utility of prolonged release of drugs is several frequently, it minimizes patient noncompliance.
folds. Prolonged release drugs are quite important in
It reduces the number and frequency of the treatment of psychoses because these
doses required. patients require medication for extended periods
It eliminates nighttime administration of of time and often show high patient
drugs. noncompliance rates. The antipsychotic

International Journal of Medical and Pharmaceutical Sciences (IJMPS) Vol 1 issue 7 www.ijmps.com Page 9
fluphenazine (R=H) has a short duration of = CO(CH2)8CH3) however have durations of
activity (6 8 h). Fluphenazine enanthate (R = activity for about one month.
CO (CH2)5 CH3) and Fluphenazine decanoate( R

N CF 3

N
.
6. Prodrugs to minimize toxicity: A
prodrug approach can be used to minimize the
toxicity associated with the drug. For example
the gastric irritation and ulcerogenicity
associated with aspirin use may result from an
N OR
accumulation of the acid in the gastric mucosal
cells. Esterification of aspirin(R = alkyl) and
other nonsteroidal anti-inflammatory agents
(NSAIDs) greatly suppresses gastric ulcerogenic
activity.

O CH3

O OR
7. Prodrugs to encourage patient acceptance:
An active drug may have an unpleasant taste
or odor, produce gastric irritation, or cause
pain when injected. The structure of the drug
could be modified to alleviate these
problems, but once administered, the prodrug
would be metabolized to the active drug.
Clindamycin causes pain on injection. The
prodrug Clindamycin phosphate is well
H3C
N CH3
NH
H3C
O
HO
H
tolerated; hydrolysis of the prodrug in vivo
occurs with a t1/2 of approximately 10
minutes. Also, Clindamycin has a bitter taste,
so it is not well accepted orally by children.
However it was found that by increasing the
chain length of 2-acetyl esters of
Clindamycin, the taste improved from
bitter(acetate ester)to no bitter taste(palmitate
ester).
CH3
Cl
O
OH SCH 3

OR
Clindamycin (R=H) Clindamycin phosphate (R=PO3H2)
8. Prodrugs to eliminate formulation colourless gas with a pungent odor that is
problems: Formaldehyde is a flammable used as a disinfectant. Solutions of high

International Journal of Medical and Pharmaceutical Sciences (IJMPS) Vol 1 issue 7 www.ijmps.com Page 10
 concentrations of formaldehyde are toxic.
Consequently it cannot be used directly in
medicine. However, the reaction of
formaldehyde with ammonia produces a
stable adamantine like solid compound,
methenamine. In acidic pH media,
methenamine hydrolyzes to formaldehyde
N
N N
N
Methenamine
Methods of Evaluation of Prodrugs21, 22:
The pharmacokinetics (ADME) of drug is
greatly influenced by physicochemical
properties such as solubility, lipophilicity, pH,
surface area, molecular weight of molecule.
Out of this pH, solubility and Lipophilicity are
the key factors in determining in vivo behavior
of drugs.
Solubility Measurement:
The solubility measurement is carried out by
placing an excess amount of mutual prodrug in
separate vials containing different solvents like
10 ml deionized water, n-hexane, phosphate
buffer of different pH etc and then stirring at
37oC for 24 hours. The solutions are centrifuged
for 5 min at 9000 rev/min and the supernatant is
filtered with cellulose acetate membrane filters.
The mutual prodrug concentration in each
filtrate is determined by suitable analytical
technique like HPAE-PAD/UV
spectroscopy/HPLC after the appropriate
dilution.
Determination of Partition Coefficients23-26:
The partition coefficient between water or buffer
and n-octanol or cyclohexane is the most widely
used measure of chemical compound
lipophilicity. Lipophilicity is a major structural
factor governing both pharmacokinetics and
pharmacodynamics of drugs. The partition
coefficient of a chemical compound provides a
International Journal of Medical and Pharmaceutical Sciences (IJMPS) Vol 1 issue 7 www.ijmps.com
and ammonium ions.Because the pH of urine
in the bladder is mildly acidic, methenamine
is used as a urinary tract antiseptic.To prevent
hydrolysis of this prodrug in the acidic
environment of the stomach the tablets are
enteric coated.
thermodynamic measure of its hydrophilicity-
lipophilicity balance.
The octanol-water partition coefficient (log P
value) of a drug substance is an indicator of
compound lipophilicity and solubility.
The log P of a compound is constant for a given
specific pair of aqueous and organic solvents.
However, the calculated log P value for a
compound in water vs. a simple organic
compound like octanol or hexane can provide a
guideline for predicting its solubility
characteristics in other aqueous and organic
solvents. The octanol-water partition coefficient
(log P value) of a drug substance is an indicator
of compound lipophilicity and solubility. The
log P value determination is a useful parameter
in Drug Discovery and Development and is used
to predict transport properties across cell
membranes, establish quantitative structure-
activity relationships (QSARs), and as an
indicator of protein binding characteristics
In vitro pH Hydrolysis study27:
Hydrolysis studies are carried out in aqueous
buffer so as to study whether the prodrug
hydrolyzes in an aqueous medium and to what
extent or not, suggesting the fate of mutual
prodrug in the system. The kinetics of hydrolysis
is monitored by the increase of free drug
concentration with time and the order of the
reaction and half-life (t1/2) are calculated. The
Page 11
rate of hydrolysis is calculated using the
equation:
Kh = (2.303/t) log (a/ax)
Where, Kh represents the hydrolysis constant, t
is the time in min, a is the initial conjugate
concentration, x is the amount of Mutual
prodrug hydrolyzed and (ax) is the amount of
the remaining prodrug. The graph between %
cumulative amounts of drug release after
hydrolysis versus time is also plotted to study
the in vitro hydrolysis of mutual prodrug.
CONCLUSION
Instead of synthesizing new compounds which is
a time consuming and too costly an affair, the
designing of derivatives of existing drug is
definitely an interesting and promising area of
research. Moreover, as the metabolic profile of
the liberated parent drug (after cleavage of the
derivative in the body) would be already known,
it could be advantageous to design derivatives of
parent drug.
Separation of therapeutic effects from toxicity is
a valuable goal in the drug development process.
Prodrug design is a part of the general drug
discovery process, in which a unique
combination of therapeutically active substances
is observed to have desirable pharmacological
effects. In human therapy prodrug designing has
given successful results in overcoming
undesirable properties like absorption,
nonspecificity, and poor bioavailability and GIT
toxicity. Thus, prodrug approach offers a wide
range of options in drug design and delivery.
The prodrug design offers a very fruitful
area of research and an efficient tool for
improving the clinical and therapeutic
effectiveness of drug that is suffering from some
undesirable side-effects hindering its clinical
usefulness otherwise.
International Journal of Medical and Pharmaceutical Sciences (IJMPS) Vol 1 issue 7 www.ijmps.com
ACKNOWLEDGMENT
Authors acknowledge the immense help
received from the scholars whose articles are
cited and included in references of this
manuscript. The authors are also grateful to
authors / editors / publishers of all those articles,
journals and books from where the literature for
this article has been reviewed and discussed.
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