1. CHITKARA UNIVERSITY
CANDIDATE'S DECLARATION
I herebycertifythat the synopsis/review whichis being presented in the project entitled “STUDY OF
PRODRUG IN SOLVING PROBLEM RELATED TO STABILITY AND BIOAVAILABILITY OF FORMULATION”
by “ASHWANI KUMAR” in partial fulfillment of requirements for the award of degree of
B.S.C(Pharmaceutical Chemistry ) submitted at Chitkara University is an authentic record of my
ownreview carried out during a period from(2014-2018) under the supervision of Mrs Garima
Signature of the Student
This is to certify that the above statement made by the candidate is correct to the best of my/our
knowledge
Signature of the Supervisor(s)
Asset. Professor (Physical pharmacy)
Chitkara University
2. STUDY OF PRODRUG IN SOLVING PROBLEM RELATED TO STABILITY AND
BIOAVAILABILITY OF FORMULATION
PROJECT REPORT
SUBMITTED IN PARTIALFULFILLMENT OF THE REQUIREMENT FOR THE AWARDOF THE DEGREE OF
B.S.C (Pharmaceutical Chemistry)
SUPERVISER SUBMITTED BY
(Univ. Roll NO )
CHITKARA UNIVERSITY
CHANDIGARH-PATIALA NATIONAL HIGHWAY(NH-64),
TEHSIL-RAJPURA, DIST-PATIALA-140401
PUNJAB
2014
4. Prodrug
Introduction:-
Prodrug is administered in a pharmacologically inactive form which is
then converted to an active form through a normal metabolic process
such as hydrolysis of an ester.
A prodrug is a precursor chemical compound of a drug. Instead of
administering a drug, a prodrug might be used instead to improve how a
medicine is absorbed, distributed, metabolized, Prodrugs are often
designed to improve bioavailability when a drug itself is poorly
absorbed from the gastrointestinal tract. A prodrug may be used to
improve how selectively the drug interacts with cells or processes that
are not its intended target. This reduces adverse or unintended effects of
a drug, especially important in treatments like which can have severe
unintended and undesirable side effects.
Classification of Prodrug:-
i) Carrier linked prodrug:-
Prodrug considered as drug containing specialized non-toxic protective
group utilized in a drug molecule, the usefulness of which is limited to
its adverse transient manner to alter or eliminate the undesirable
properties of parent drug molecule. In this type of prodrug, the active
drug is covalently linked to an inert carrier or transport moiety. Such
prodrug has modified lipophilicity due to attached carrier. The active
drug is released by hydrolytic cleavage either chemically or
enzymaticaly. The used moiety is ester or amides (Bagshawe, KD 1993,
Sharma SK, 1992).The unique feature of this approach is that the
physicochemical properties can be tailored by means of changing
thestructure of the promoiety.An illustrative example is dipivefrine the
prodrug of epinephrine.
5. ii) Mutual prodrugs:-
Two pharmacological agents are coupled together so that each
act as a promoiety for another such derivatives has been termed
as mutual prodrug. e.g. benorylate is a mutual prodrug of aspirin
and paracetamol, therefore, used to treat chronic inflammation at
a decreased dosage and at reduced risk of irritation(Rautio J, et
al., 1998).
iii) Bioprecursors prodrugs:-
These are obtained by chemical modification of active drug but
do not contain a carrier. Such type of prodrug has almost the
same lipophilicity as the parent drug and is bioactivated
generally by redox biotransformation.
Bioprecursors prodrugs contain no promoiety but rather relies
upon metabolism to introduce the necessary functionality to
create an active species e.g. NSAID sulindac is active as the
sulfoxide and must be reduced metabolically to active sulfide.
Administration of the inactive form has the benefit of reducing
the git irritation associated with the sulfide. e.g. phenylbutazone
a bioprecursor of oxyphenbutazone(Jones G.,1985).
iv) Trepartate Prodrugs:-
Structures of most prodrugs are bipurtate in nature in which the
parent drug is attached directly to promoiety. However in some
cases bipartate prodrug may be unstable due to inherent nature
of the drug promoiety bond. This problem can be overcome by
designing a tripartate prodrug utilizing a spacer or connector
group between the drug and promoiety. The spacer or connector
must be designed in such a way that the initial activation is
followed by spontaneous cleavage of remaining drug spacer
6. bond under physiological conditions to release parent drug.
v) Macromolecular Prodrugs:-
Study of prodrug in solving problem related to
stability :-
INTRODUCTION OF STABILITY:-
Stability of drug can be defined as the time from the
date of manufacture and packaging of the
formulation until its chemical or predetermined level
of labeled potency and it physical characteristics not
changed appreciably stability.
PHYSICAL CHANGES OF STABILITY:-
1) Appearance
2) Melting point
3) Clarity and colour of solution
4) Moisture
5) Crystal modification
7. 6) Particle size chemical changes
7) Increase in degradation
8) Decrease of assay
