THE PRODRUG DESIGNING FOR NEW SELECTION AND FORMULATION OF DRUG COMPATIBLE WITH API I.E. ACTIVE PHARMACUTICAL INGREDIENT, AND ITS EFFECT WHICH SHOULD BE 0. THE DRUG COMBINED WITH API AND AVILABLE IN MARKET AND DRUGS NEED TO BE COMBINE ARE ALSO DISCUSSED WITH ITS STRUCTURE AND SAR, AND COVERED AS PER THE SYLLABUS OF PCI.
PEPTIDOMIMETICS , HERE WE HAVE INCLUDED THE INTRODUCTION, CLASSIFICATION, ADVANTAGES , DISADVANTAGES, ITS METHODS PREPARATION, PRINCIPLES OD DRUG DESIGN, ITS CHEMISTRY. STEREOCHEMISTRY, SYNTHESIS AND APPLICATIONS
Stereochemistry is the ‘chemistry of space’ , that is stereochemistry deals with the spatial arrangements of atoms and groups in a molecule.
Stereochemistry can trace its roots to the year 1842 when the French chemist Louis Pasteur made an observation that the salts of tartaric acid collected from a wine production vessel have the ability to rotate plane-polarized light, whereas the same salts from different sources did not have this ability.
Isomers are compounds that contain exactly the same number of atoms, i.e., they have exactly the same empirical formula, but differ from each other by the way in which the atoms are arranged.
Constitutional isomers, also known as structural isomers, are specific types of isomers that share the same molecular formula but have different bonding atomic organization and bonding patterns.
Stereoisomers are molecules having the same molecular formula and the atomic arrangement, but differ in their spatial arrangement.
Geometric isomers are two or more coordination compounds which contain the same number and types of atoms, and bonds (i.e., the connectivity between atoms is the same), but which have different spatial arrangements of the atoms.
There are 2 types of geometric isomers, ‘cis’ and ‘trans’.-cis isomers: when similar groups are present on the same side of the double bonds, then they are termed as cis.- trans isomers: when similar groups are present on the opposite sides of the double bonds then they are called trans isomers.
cis-diethylstilbestrol has only 7% of the estrogenic activity of trans-diethylstilbesterol.
Cisplatin have anticancer activity where ae trans platin is an inactive compound.
In chemistry, a molecule or ion is called chiral if it cannot be superposed on its mirror image by any combination of rotations, translations, and some conformational changes.
Chirality is the property of being non identical to ones mirror image.
Chiral center is defined as the atom bearing 4 different atoms or group of atoms.
Molecules that form nonsuperimposable mirror images, and thus exist as enantiomers, are said to be chiral molecules.
For a molecule to be chiral, it cannot contain a plane of symmetry.
The term enantioselectivity refers to the efficiency with which the reaction produces one enantiomer.
Enantiomers are stereoisomers that are non-superimposable mirror images.
Have identical properties.
Similar shapes
Diastereomers are stereoisomers that are non superimposable and are not mirror images.
Have distinct physical properties.
Have different molecular shapes.
Enantiomers consist of a pair of molecules that are mirror images of each other and are not superimposable.
When a molecule contains only one chiral centre , the two stereoisomers are known as enantiomers.
These may be referred to or labelled using the configurational descriptors as either:
R(rectus meaning right handed) or S(sinister meaning left handed),
D(dextrorotatory)or L (laevorotatory)
E-Entgegen or Z- Zusamen
THE PRODRUG DESIGNING FOR NEW SELECTION AND FORMULATION OF DRUG COMPATIBLE WITH API I.E. ACTIVE PHARMACUTICAL INGREDIENT, AND ITS EFFECT WHICH SHOULD BE 0. THE DRUG COMBINED WITH API AND AVILABLE IN MARKET AND DRUGS NEED TO BE COMBINE ARE ALSO DISCUSSED WITH ITS STRUCTURE AND SAR, AND COVERED AS PER THE SYLLABUS OF PCI.
PEPTIDOMIMETICS , HERE WE HAVE INCLUDED THE INTRODUCTION, CLASSIFICATION, ADVANTAGES , DISADVANTAGES, ITS METHODS PREPARATION, PRINCIPLES OD DRUG DESIGN, ITS CHEMISTRY. STEREOCHEMISTRY, SYNTHESIS AND APPLICATIONS
Stereochemistry is the ‘chemistry of space’ , that is stereochemistry deals with the spatial arrangements of atoms and groups in a molecule.
Stereochemistry can trace its roots to the year 1842 when the French chemist Louis Pasteur made an observation that the salts of tartaric acid collected from a wine production vessel have the ability to rotate plane-polarized light, whereas the same salts from different sources did not have this ability.
Isomers are compounds that contain exactly the same number of atoms, i.e., they have exactly the same empirical formula, but differ from each other by the way in which the atoms are arranged.
Constitutional isomers, also known as structural isomers, are specific types of isomers that share the same molecular formula but have different bonding atomic organization and bonding patterns.
Stereoisomers are molecules having the same molecular formula and the atomic arrangement, but differ in their spatial arrangement.
Geometric isomers are two or more coordination compounds which contain the same number and types of atoms, and bonds (i.e., the connectivity between atoms is the same), but which have different spatial arrangements of the atoms.
There are 2 types of geometric isomers, ‘cis’ and ‘trans’.-cis isomers: when similar groups are present on the same side of the double bonds, then they are termed as cis.- trans isomers: when similar groups are present on the opposite sides of the double bonds then they are called trans isomers.
cis-diethylstilbestrol has only 7% of the estrogenic activity of trans-diethylstilbesterol.
Cisplatin have anticancer activity where ae trans platin is an inactive compound.
In chemistry, a molecule or ion is called chiral if it cannot be superposed on its mirror image by any combination of rotations, translations, and some conformational changes.
Chirality is the property of being non identical to ones mirror image.
Chiral center is defined as the atom bearing 4 different atoms or group of atoms.
Molecules that form nonsuperimposable mirror images, and thus exist as enantiomers, are said to be chiral molecules.
For a molecule to be chiral, it cannot contain a plane of symmetry.
The term enantioselectivity refers to the efficiency with which the reaction produces one enantiomer.
Enantiomers are stereoisomers that are non-superimposable mirror images.
Have identical properties.
Similar shapes
Diastereomers are stereoisomers that are non superimposable and are not mirror images.
Have distinct physical properties.
Have different molecular shapes.
Enantiomers consist of a pair of molecules that are mirror images of each other and are not superimposable.
When a molecule contains only one chiral centre , the two stereoisomers are known as enantiomers.
These may be referred to or labelled using the configurational descriptors as either:
R(rectus meaning right handed) or S(sinister meaning left handed),
D(dextrorotatory)or L (laevorotatory)
E-Entgegen or Z- Zusamen
Introduction
Classification
Therapeutic values of peptidomimetics
Design of peptidomimetics by manipulation of amino acids
Modification of peptide backbone
Chemistry of prostaglandins, leukotrienes and thromboxanes
Chemistry of Prostaglandins, leukotrienes and thromboxanes(Advance medicinal ...Rohit kaushiK.
1st discovered in human serum in 1930, were found to be stimulate uterine contraction and reduce pressure.
Presumed to be synthesized by prostate gland hence the name.
Later found that synthesized in all tissue except erythrocytes.
It have a cyclopentane ring (formed from 8 to 12 carbon atoms) and two side chains, with carboxyl group on one side.
They differ In their structure due to substituent group double bond on cyclopentane ring.
Prostaglandins are structurally resemble with prostanoic acid, 20-carbon fatty acid.
Abbreviated as PG, with the class designated by a capital letter A,B,D,E,F,G,H and I, followed by a number.
PGE and PGF; 1st isolated from the biological fluids.
The letters refer to the different ring structure, except in PGG and PGH: same ring structure (cyclo endohydroperoxide).
In the same series, depending upon double bonds on the side chains designated as PGE1, PGE2, PGE3..etc
The number of double bonds varies from 1-3.
PROSTAGLANDINS RECEPTORS
They function close to the site of synthesis and are deactivated to inactive metabolites before moving into the circuation.
Act locally in very low concentration, and acts on GPCR receptors.
INHIBITION OF PROSTAGLANDINS
Corticosteroids (e.g. cortisol) prevent the formation of arachidonic acid by inhibiting the enzyme phospholipase A2.
Anti inflammatory drugs inhibits the synthesis of prostaglandins.
They block the action of cyclooxygenase.
Aspirin irreversibly inhibits cyclooxygenase.
DEGRADATION OF PROSTAGLANDINS
All eicosanoids are metabolized rapidly.
Degradation mainly occurs in liver and lung.
Two enzymes, namely 15-α-hydroxy PG dehydrogenase & 13-PG reductase, convert hydroxyl group at C15 to keto group & then to C13 and C14 dihydroderivative.
BIOCHEMICAL ACTION OF PROSTAGLANDINS
The Prostaglandins (PGE, PGA, & PGI2) are vasodilator in nature. So they decreases blood pressure.
PGE1 & PGE2 induce the symptoms of inflammation (redness, swelling, edema etc.) due to arteriolar vasodilator, and cause rheumatoid arthritis, psoriasis etc. so Corticosteroids are used to treat these conditions.
PGE2 & PGF2 are used for the medical termination of pregnancy and induction of labor.
Pyrogens (fever causing) promote PG synthesis leading to the formation of PGE2.
Migraine is also due to PGE2.
PGE2 along with histamine and bradykinin causes pain.
PGI2 inhibit platelet aggregation.
They are used in the treatment of gastric ulcers, hyoertention, thrombosis, asthma etc.
Prostaglandins are also employed in the medical termination of pregnancy, prevention of conception, induction of labor etc.
Leukotrienes are synthesized by leucocytes, mast cells, lung, heart, spleen etc. by lipoxygenase pathway of arachidonic acid.
Leukotrienes are 20- Carbon polyenoic fatty acids having a number of substituents.
Depending upon the substitutions, they are divided into LTA, LTB, LTD, and LTE.
Each type is divided into sub-groups depending upon the number of double bonds which vary from 3-5.
Leukotrienes possess
There are many ways that drug-resistant infections can be prevented: immunization, safe food preparation, handwashing, and using antibiotics as directed and only when necessary. In addition, preventing infections also prevents the spread of resistant bacteria.The main cause of antibiotic resistance is antibiotic use. When we use antibiotics, some bacteria die but resistant bacteria can survive and even multiply. The overuse of antibiotics makes resistant bacteria more common. The more we use antibiotics, the more chances bacteria have to become resistant to them.
stereochemistry and drug action ; basic introduction about stereochemistry and stereoisomers ; pharmacokinetic and pharmacodynamics concept of stereochemistry ; easson Stedman hypothesis ; stereo selectivity criteria .
Single liposomes and vesicles are successfully utilized as delivery vehicles of pharmaceuticals. However limitations of these unilamellar, single compartments led to the development of encapsulated multicompartment systems that establishes the prospect of multicomponent or multifunctional drug delivery systems. So far compartmentalization is restricted to binary systems. To realize a personalized drug delivery, a programmable linkage of n-entities of different content will be needed. Here we present both a programmable DNA-mediated linkage of three distinct vesicle populations and a novel encapsulation protocol. We discuss how the techniques established in this study might be used in personalized healthcare based on custom tailored encapsulated multicompartment vesicular drug delivery systems.
TOWARDS PERSONALIZED DRUG DELIVERY – Preparation of an Encapsulated Multicompartment System. Third International Conference on Biomedical Electronics and Devices (BIODEVICES 2010), Valencia, Spain (20-23 January, 2010), 30 minutes oral presentation.
Introduction
Classification
Therapeutic values of peptidomimetics
Design of peptidomimetics by manipulation of amino acids
Modification of peptide backbone
Chemistry of prostaglandins, leukotrienes and thromboxanes
Chemistry of Prostaglandins, leukotrienes and thromboxanes(Advance medicinal ...Rohit kaushiK.
1st discovered in human serum in 1930, were found to be stimulate uterine contraction and reduce pressure.
Presumed to be synthesized by prostate gland hence the name.
Later found that synthesized in all tissue except erythrocytes.
It have a cyclopentane ring (formed from 8 to 12 carbon atoms) and two side chains, with carboxyl group on one side.
They differ In their structure due to substituent group double bond on cyclopentane ring.
Prostaglandins are structurally resemble with prostanoic acid, 20-carbon fatty acid.
Abbreviated as PG, with the class designated by a capital letter A,B,D,E,F,G,H and I, followed by a number.
PGE and PGF; 1st isolated from the biological fluids.
The letters refer to the different ring structure, except in PGG and PGH: same ring structure (cyclo endohydroperoxide).
In the same series, depending upon double bonds on the side chains designated as PGE1, PGE2, PGE3..etc
The number of double bonds varies from 1-3.
PROSTAGLANDINS RECEPTORS
They function close to the site of synthesis and are deactivated to inactive metabolites before moving into the circuation.
Act locally in very low concentration, and acts on GPCR receptors.
INHIBITION OF PROSTAGLANDINS
Corticosteroids (e.g. cortisol) prevent the formation of arachidonic acid by inhibiting the enzyme phospholipase A2.
Anti inflammatory drugs inhibits the synthesis of prostaglandins.
They block the action of cyclooxygenase.
Aspirin irreversibly inhibits cyclooxygenase.
DEGRADATION OF PROSTAGLANDINS
All eicosanoids are metabolized rapidly.
Degradation mainly occurs in liver and lung.
Two enzymes, namely 15-α-hydroxy PG dehydrogenase & 13-PG reductase, convert hydroxyl group at C15 to keto group & then to C13 and C14 dihydroderivative.
BIOCHEMICAL ACTION OF PROSTAGLANDINS
The Prostaglandins (PGE, PGA, & PGI2) are vasodilator in nature. So they decreases blood pressure.
PGE1 & PGE2 induce the symptoms of inflammation (redness, swelling, edema etc.) due to arteriolar vasodilator, and cause rheumatoid arthritis, psoriasis etc. so Corticosteroids are used to treat these conditions.
PGE2 & PGF2 are used for the medical termination of pregnancy and induction of labor.
Pyrogens (fever causing) promote PG synthesis leading to the formation of PGE2.
Migraine is also due to PGE2.
PGE2 along with histamine and bradykinin causes pain.
PGI2 inhibit platelet aggregation.
They are used in the treatment of gastric ulcers, hyoertention, thrombosis, asthma etc.
Prostaglandins are also employed in the medical termination of pregnancy, prevention of conception, induction of labor etc.
Leukotrienes are synthesized by leucocytes, mast cells, lung, heart, spleen etc. by lipoxygenase pathway of arachidonic acid.
Leukotrienes are 20- Carbon polyenoic fatty acids having a number of substituents.
Depending upon the substitutions, they are divided into LTA, LTB, LTD, and LTE.
Each type is divided into sub-groups depending upon the number of double bonds which vary from 3-5.
Leukotrienes possess
There are many ways that drug-resistant infections can be prevented: immunization, safe food preparation, handwashing, and using antibiotics as directed and only when necessary. In addition, preventing infections also prevents the spread of resistant bacteria.The main cause of antibiotic resistance is antibiotic use. When we use antibiotics, some bacteria die but resistant bacteria can survive and even multiply. The overuse of antibiotics makes resistant bacteria more common. The more we use antibiotics, the more chances bacteria have to become resistant to them.
stereochemistry and drug action ; basic introduction about stereochemistry and stereoisomers ; pharmacokinetic and pharmacodynamics concept of stereochemistry ; easson Stedman hypothesis ; stereo selectivity criteria .
Single liposomes and vesicles are successfully utilized as delivery vehicles of pharmaceuticals. However limitations of these unilamellar, single compartments led to the development of encapsulated multicompartment systems that establishes the prospect of multicomponent or multifunctional drug delivery systems. So far compartmentalization is restricted to binary systems. To realize a personalized drug delivery, a programmable linkage of n-entities of different content will be needed. Here we present both a programmable DNA-mediated linkage of three distinct vesicle populations and a novel encapsulation protocol. We discuss how the techniques established in this study might be used in personalized healthcare based on custom tailored encapsulated multicompartment vesicular drug delivery systems.
TOWARDS PERSONALIZED DRUG DELIVERY – Preparation of an Encapsulated Multicompartment System. Third International Conference on Biomedical Electronics and Devices (BIODEVICES 2010), Valencia, Spain (20-23 January, 2010), 30 minutes oral presentation.
Prodrugs an approach to solve problems related to admeJyotsna Patil
prodrugs an approach to overcome problems related to ADME, for MPharm students
sub- modern pharmaceutical and medicinal chemistry
branch- quality assurance
ABSTRACT
The parenteral administration route is the most effective and common form of delivery for active drug substances with poor bioavailability and the drugs with a narrow therapeutic index. Drug delivery technology that can reduce the total number of injection throughout the drug therapy period will be truly advantageous not only in terms of compliance, but also to improve the quality of the therapy and also may reduce the dosage frequency. Such reduction in frequency of drug dosing is achieved by the use of specific formulation technologies that guarantee the release of the active drug substance in a slow and predictable manner. The development of new injectable drug delivery system has received considerable attention over the past few years. A number of technological advances have been made in the area of parenteral drug delivery leading to the development of sophisticated systems that allow drug targeting and the sustained or controlled release of parenteral medicines.
Basic concepts of Prodrug & their application in pharmacy fieldsSHUVAM SAR
Definition of prodrugs along with their uses in pharmacy have been discusses here in brief. Also includes the basic objectives of their formulation with examples.
The classical approach for prodrug design uses the non-specific strategy of covalently modifying the drug of interest by attaching hydrophilic functionalities
- Routes of administration
- First pass metabolism, bioavailablilty, drug distribution,
- Drug interactions with proteins, Drug metabolism, elimination, Half-life
Pharmaceutical Inorganic Chemistry
Unit I Chapter 2
Different official waters used in pharmaceuticals
Potable water
Purified water
Water for injection
Sterile water for injection
Bacteriostatic water for injection
Different parameters for waters
Acids bases and buffers
Pharmaceutical Inorganic Chemistry
Unit 2, Chapter 1
Arrhenius, Bronsted-Lowry and Lewis Concepts of Acids and bases,
Concept of pH, pOH, pKa, pKb
Concept of buffers, buffer solutions, buffer action, and buffer capacity,
Buffer equation
Buffers in pharmaceuticals
Buffered isotonic solutions
Measurement and adjustment of tonicity
the power point presentation describes how Information technology and especially chem-informatics has revolutionised and simplified the process of drug design and discovery
Ion pair chromatography for pharmacy studentsabhishek rai
Ion-PairChromatography
A GENERALISED OVERVIEW
Chromatography
HPLC
Reverse Phase Chromatography
Ion Pair Chromatography
Ion Pair Reagent
Mechanism of Ion Pair Chromatography
Ion Pair Wash Procedure
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
Best Ayurvedic medicine for Gas and IndigestionSwastikAyurveda
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
2. • Prodrug
• Aim of prodrug design
• Objectives of prodrug research
• Classification
• Carrier linked prodrugs
• Bioprecursor prodrugs
• Steps in prodrug design
• Applications
3. • pharmacologically inert chemical derivative that can be converted in
vivo, enzymatically and/or a chemical transformation, to the active
drug that exerts the intended therapeutic effect(s).
• Bio-reversible derivatives of drug molecules.
• Ideally, the prodrug should be converted to the parent drug as soon
as it reach its goal, and then followed by the subsequent rapid
metabolism and/or elimination of the released active group
4. • To mask undesirable drug properties, such as:
– Physical Properties
– Poor aqueous solubility
– Low lipophilicity
– low target selectivity,
– chemical instability,
– undesirable taste,
– irritation or pain after local administration,
– presystemic metabolism and
– toxicity.
– Pharmacokinetic Properties
– Poor distribution across biological membranes
– Good substrate for first-pass metabolism
– Rapid absorption/excretion when long-term effect desired
– Not site-specific
5. • To optimize:
– absorption,
– distribution,
– metabolism,
– excretion, and
– unwanted toxicity of the parent drugs.
6. • According to Testa there are three basic, overlapping objectives in
prodrug research:
• 1. Pharmaceutical: to improve solubility, chemical stability, and
organoleptic properties; to decrease irritation and/or pain after local
administration, to reduce problems related with the pharmaceutical
technology of the active agent.
• 2. Pharmacokinetic: to improve absorption (oral and by non-oral
routes), to decrease presystemic metabolism to improve time profile,
to increase organ/ tissue-selective delivery of the active agent.
• 3. Pharmacodynamic: to decrease toxicity and improve therapeutic
index, to design single chemical entities combining two drugs.
7. • Classified into :-
– Carrier Linked Prodrug: the active agent is attached through
the metabolically labile linkage to a carrier or promoiety which
is not necessary for the activity, but may impart some desirable
properties of the drug.
– Bioprecursor: contain no promoiety but is rather reliant on the
metabolism by processes such as oxidation, reduction,
phosphorylation, and sulfation activations to introduce the
functionality necessary to create the desired active agent unlike
the hydrolytic activation of the carrier-linked prodrugs.
8. • Bipartate Prodrug
– This prodrug consists of the active drug covalently linked to an
inert carrier or transport moiety, generally ester or amide.
– Have greatly modified lipophilicity due to the attached carrier.
– The active drug is released by hydrolytic cleavage either
chemically or enzymatically.
9. • Tripartate Prodrug
– Drug moiety is not directly attached to the carrier moiety.
– First the drug moiety is attached with the linker and then this
linker is attached with carrier.
10. • Mutual Prodrug
– Carrier used is another biologically active drug instead of some
inert molecule.
– A mutual prodrug consists of two pharmacologically active
agents which are coupled together in such a way to act as a
promoiety for the other agent and vice versa.
– The carrier selected may have the same biological action as that
of the parent drug and thus might give synergistic action, or the
carrier may have some additional biological action that is lacking
in the parent drug, thus ensuring some additional benefit.
11. • Bioprecursor prodrugs do not include any carrier molecule.
• An inactive drug undergoes chemical modification to convert into a
compound which itself is active drug or further metabolized into
active form which have a desired therapeutic efficacy.
• The chemical reactions which can occur in this process include
oxidation, reduction, phosphorylation, or sulfation .
12. Following steps to be followed for designing a prodrug:
– Identification of drug delivery problem
– Identification of desired physicochemical properties
– Selection of transport moiety which will give prodrug desired
transport properties be readily cleaved in the desired biological
compartment.
13. Brain Targeting
Colon Targeting
To enhance aqueous solubility
Odour masking
Reduction of gastrointestinal irritation
Drug targeting
Reduction of stability problem
Increase in patient compliance
14. • BRAIN TARGETING
– The hydrophilic drugs can not be administered as such in the brain
and thus the therapeutic efficacy cannot be achieved.
– The hydrophilic drugs can be converted into their lipophilic forms to
achieve the goal but this leads to the systemic toxicity due to the
penetration of drugs into the other tissues.
– Eg,
• Dihydropridine pyridinium type redox system was developed for brain
specific sustained delivery of drug.
• The drug containing amine group is made lipophilic by coupling to
dihydropyridine promoiety that facilitate penetration of prodrug through
the blood brain barrier.
• In the CNS, dihydropridine group converted to polar pyridinium salt, thus
becomes poorly permeable to blood brain barrier and thus remain at the
site and cleavage provides sustained release for action.
15. • COLON TARGETING
– For sulphasalazine formed by coupling of diazotized
sulphanilamide pyridine with 5-amino salicylicacid (ASA).
– On oral administration, intact sulphasalazine reaches the colon.
The azo reductase associated with colonic microflora convert
sulphasalazin to its constituents entities, the active species 5ASA
available for absorption in colon, while precolonic absorption
responsible for side effects is reduced.
• TO ENHANCE AQUEOUS SOLUBILITY
– Prednisolone is a poorly aqueous soluble drug which should be
converted into water soluble form for their delivery into the
body.
– prodrug prednisolone phosphate is prepared which is activated
in vivo by the phosphotase.
16. • Odour masking
– The odour of a compound is due to its vapour pressure.
Compounds with Low boiling point will have a strong odour.
– Eg,
• Ethyl mercapta have a Foul smell is a liquid of boiling point 35°C useful
in the treatment of leprosy.
• Its foul smell is removed by converting it into its phthalate ester, diethyl
isophthalate, which has higher boiling point and odorless.
• The prodrug is administered by rubbing on the skin, after absorption, the
ester is metabolized to parent drug by thioesterase.
• Reduction of gastrointestinal irritation
– Many drugs react with the acid secretion in stomach and causes
gastric irritation for e.g NSAIDS.
– In case of NSAIDS, this problem can be overcome by
preparation of prodrug salsalates.
17. • Reduction of stability problem
– Most of the drugs may be rapidly metabolized and rendered
inactive before it reaches the site of action.
– The structure may be modified to block the metabolism until the
drug is at the desired site.
– Some prodrugs protect the drug from first-pass effect. e.g:
Propranolol.
• It is a widely used antihypertensive drug, but its oral bioavalability
is very low because of first pass metabolism.
• The hemisuccinate ester of propranolol was prepared to block
glucuronide formation. Hence oral administration of propranolol
hemisuccinate elevates plasma levels of propranolol for about 8
times.
18. • Drug targeting
– The distribution of drug to non targeted tissues causes toxicity
and reduction of drug concentration in the target tissues due to
which optimum therapeutic action can not be achieved.
– So for obtaining desired therapeutic action drug targeting is
necessary and this can be easily achieved by prodrug approach.
• Increase in patient compliance
– Many drugs have unpleasant taste, odour and some may causes
GIT irritation and when given in form of injection causes pain.
These problems cause poor patient compliance.