Phsicochemical properties according to pci syllubus.
The ability of a chemical compound to elicit a pharmacological/ therapeutic effect is related to the influence of various physical and chemical (physicochemical) properties of the chemical substance on the bio molecule that it interacts with.
1)Physical Properties : Physical property of drug is responsible for its action
2)Chemical Properties :The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
DEFINITION:
The ability of a chemical compound to elicit a pharmacological/ therapeutic effect is related to the influence of various physical and chemical (physicochemical) properties of the chemical substance on the bio molecule that it interacts with.
1)Physical Properties
Physical property of drug is responsible for its action 2)Chemical Properties
The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
Various Physico-Chemical Properties are,
Solubility Partition Coefficient
Dissociation constant Hydrogen Bonding Ionization of Drug Redox Potential Complexation Surface activity Protein binding Isosterism
1. Solubility:
• The solubility of a substance at a given temperature is defined as the concentration of the dissolved solute, which is in equillibrium with the solid solute.
• Solubility depends on the nature of solute and solvent as well as temperature , pH & pressure.
• The solubility of drug may be expressed in terms of its affinity/philicity or repulsion/phobicity for either an aqueous or organic solvent.
The atoms and molecules of all organic substances are held together by various types of bonds (e.g. hydrogen bond, dipole –dipole, ionic bond etc.)
These forces are involved in solubility because it is the solvent-solvent, solute-solute, solvent-solute interactions that governs solubility.
Methods to improve solubility of drugs
1) Structural modification (alter the structure of molecules) 2) Use of Cosolvents (Ethanol, sorbitol,PPG,PEG)
3) Employing surfactants 4) Complexation
Importance of solubility
1. Solubility concept is important to pharmacist because it govern the preparation of liquid dosage form and the drug must be in solution before it is absorbed by the body to produce the biological activity.
2. Drug must be in solution form to interact with receptors.
Phsicochemical properties according to pci syllubus.
The ability of a chemical compound to elicit a pharmacological/ therapeutic effect is related to the influence of various physical and chemical (physicochemical) properties of the chemical substance on the bio molecule that it interacts with.
1)Physical Properties : Physical property of drug is responsible for its action
2)Chemical Properties :The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
DEFINITION:
The ability of a chemical compound to elicit a pharmacological/ therapeutic effect is related to the influence of various physical and chemical (physicochemical) properties of the chemical substance on the bio molecule that it interacts with.
1)Physical Properties
Physical property of drug is responsible for its action 2)Chemical Properties
The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
Various Physico-Chemical Properties are,
Solubility Partition Coefficient
Dissociation constant Hydrogen Bonding Ionization of Drug Redox Potential Complexation Surface activity Protein binding Isosterism
1. Solubility:
• The solubility of a substance at a given temperature is defined as the concentration of the dissolved solute, which is in equillibrium with the solid solute.
• Solubility depends on the nature of solute and solvent as well as temperature , pH & pressure.
• The solubility of drug may be expressed in terms of its affinity/philicity or repulsion/phobicity for either an aqueous or organic solvent.
The atoms and molecules of all organic substances are held together by various types of bonds (e.g. hydrogen bond, dipole –dipole, ionic bond etc.)
These forces are involved in solubility because it is the solvent-solvent, solute-solute, solvent-solute interactions that governs solubility.
Methods to improve solubility of drugs
1) Structural modification (alter the structure of molecules) 2) Use of Cosolvents (Ethanol, sorbitol,PPG,PEG)
3) Employing surfactants 4) Complexation
Importance of solubility
1. Solubility concept is important to pharmacist because it govern the preparation of liquid dosage form and the drug must be in solution before it is absorbed by the body to produce the biological activity.
2. Drug must be in solution form to interact with receptors.
This is the presentation for B. Pharm. IV semester students.
It includes Introduction of Medicinal Chemistry, History and Development of Medicinal Chemistry
This powerpoint presentation will help to know about introduction of bioisosterism by Biotechnology point of view. Hope this powerpoint presentation will your reference.
Physico-chemical Properties in Relation of Drug actionPradnya Gondane
This is the presentation for B. Pharm. IV semester students. It includes all the physico-chemical properties which affect drug action like solubility, ionization, pH, pKa, Protein Binding, Chelation, Hydrogen Bonding, Partition Coefficient and steric factors which includes, optical, conformational and bio isosters. This is prepared according to the PCI syllabus for B. Pharm. IV Semester students for Subject Medicinal Chemistry-I
1)Physical Properties
Physical property of drug is responsible for its action
2)Chemical Properties
The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
Introduction
Mechanisms of protein drug binding
Kinetics of protein drug binding
Classes of protein drug binding.
1. Binding of drug to blood components.
(a) Plasma proteins
(b) Blood cells
2. Binding of drug to extravascular tissue protein
Determination of Protein-drug Binding
Factors affecting protein drug binding
Significance of protein/tissue binding of drug
The ability of a chemical compound to elicit a pharmacological/ therapeutic effect is related to the influence of various physical and chemical (physicochemical) properties of the chemical substance on the bio molecule that it interacts with.
1)Physical Properties : Physical property of drug is responsible for its action
2)Chemical Properties :The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
This is the presentation for B. Pharm. IV semester students.
It includes Introduction of Medicinal Chemistry, History and Development of Medicinal Chemistry
This powerpoint presentation will help to know about introduction of bioisosterism by Biotechnology point of view. Hope this powerpoint presentation will your reference.
Physico-chemical Properties in Relation of Drug actionPradnya Gondane
This is the presentation for B. Pharm. IV semester students. It includes all the physico-chemical properties which affect drug action like solubility, ionization, pH, pKa, Protein Binding, Chelation, Hydrogen Bonding, Partition Coefficient and steric factors which includes, optical, conformational and bio isosters. This is prepared according to the PCI syllabus for B. Pharm. IV Semester students for Subject Medicinal Chemistry-I
1)Physical Properties
Physical property of drug is responsible for its action
2)Chemical Properties
The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
Introduction
Mechanisms of protein drug binding
Kinetics of protein drug binding
Classes of protein drug binding.
1. Binding of drug to blood components.
(a) Plasma proteins
(b) Blood cells
2. Binding of drug to extravascular tissue protein
Determination of Protein-drug Binding
Factors affecting protein drug binding
Significance of protein/tissue binding of drug
The ability of a chemical compound to elicit a pharmacological/ therapeutic effect is related to the influence of various physical and chemical (physicochemical) properties of the chemical substance on the bio molecule that it interacts with.
1)Physical Properties : Physical property of drug is responsible for its action
2)Chemical Properties :The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
Physico chemical properties of drugs-convertedN J V S Pavan
this presentation is about the physico-chemical properties of a drug which are the reason for the drug's therapeutic effects and pharmacokinetics , pharmacodynamics ...
the information in the presentation is very much useful for the b.pharm 4th sem students .
Students can easily understand the concept as the presentation contains many examples
Introduction:
History & Development:
Physicochemical Properties in relation to biological action:
Ionization
Solubility
Partition Coefficient
Hydrogen Bonding:
Protein Binding:
Chelation:
Bioisosterism:
Optical & Geomentrical Isomerism
Drug Metabolism:
Drug Metabolism Principles: Phase I & Phase II
Factors Affecting Drug Metabolism including steriochemical Aspects
Biopharmaceutic considerations in Drug Product DesignRiaz Islam
Drug product Design remain one of the most challenging aspects in formulation development. But nowadays formulation strategies have been far more successful in improving the bioavailability of the compounds with poor solubility, poor dissolution rate, and poor chemical stability in acidic environment. This article begins with a brief discussion on Physical and Chemical Properties of the Drug Impacting Oral Absorption. This article also reviews the Factors Contributing to Poor Aqueous Solubility. and a brief relationship between Physicochemical Properties and Drug Delivery System.
This is a presentation by Dada Robert in a Your Skill Boost masterclass organised by the Excellence Foundation for South Sudan (EFSS) on Saturday, the 25th and Sunday, the 26th of May 2024.
He discussed the concept of quality improvement, emphasizing its applicability to various aspects of life, including personal, project, and program improvements. He defined quality as doing the right thing at the right time in the right way to achieve the best possible results and discussed the concept of the "gap" between what we know and what we do, and how this gap represents the areas we need to improve. He explained the scientific approach to quality improvement, which involves systematic performance analysis, testing and learning, and implementing change ideas. He also highlighted the importance of client focus and a team approach to quality improvement.
Ethnobotany and Ethnopharmacology:
Ethnobotany in herbal drug evaluation,
Impact of Ethnobotany in traditional medicine,
New development in herbals,
Bio-prospecting tools for drug discovery,
Role of Ethnopharmacology in drug evaluation,
Reverse Pharmacology.
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
For more information, visit-www.vavaclasses.com
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
In this webinar you will learn how your organization can access TechSoup's wide variety of product discount and donation programs. From hardware to software, we'll give you a tour of the tools available to help your nonprofit with productivity, collaboration, financial management, donor tracking, security, and more.
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
Model Attribute Check Company Auto PropertyCeline George
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Instructions for Submissions thorugh G- Classroom.pptxJheel Barad
This presentation provides a briefing on how to upload submissions and documents in Google Classroom. It was prepared as part of an orientation for new Sainik School in-service teacher trainees. As a training officer, my goal is to ensure that you are comfortable and proficient with this essential tool for managing assignments and fostering student engagement.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
2. DEFINITION
The ability of a chemical compound to elicit (evoke or
draw out) a pharmacological/therapeutic effect is related
to the influence of various physical and chemical
(physicochemical) properties of the chemical substance on
the bio-molecule that it interacts with.
1) Physical Properties
Physicalproperty ofdrug isresponsiblefor its action
2) Chemical Properties
The drug react extracellularly according to simple
chemical reactions likeneutralization, chelation,
oxidation etc.
3. Types of Physico-Chemical Properties:
1. Ionization of Drug
2. Solubility
3. Partition Coefficient
4. Hydrogen Bonding
5. Protein binding
6. Isosterism
7. Chelation
8. Optical Isomerism
9. Geometrical isomerism
4. 1. Ionization of drug
Most of the drugs are either weak acids or base and can exist in
either ionised or unionised state.
Ionization = Protonation or deprotonation resulting in charged
molecules.
The ionization of the drug depends on its pKa & pH.
The rate of drug absorption is directly proportional to the
concentration of the drug at absorbable form but not the
concentration of the drug at the absorption site.
Ionization form imparts good water solubility to the drug which
is required of binding of drug and receptor interaction
Unionized form helps the drug to cross the cell membrane.
Example - Barbituric acid is inactive because it is strong acid.
while, 5,5 disubstituted Barbituric acid has CNS depressant
action because it is weak acid.
5. H A + H 2 O ↔ H 3 O + A -
U n i o n i z e d
A c i d
C o n j u g a t e
a c i d
C o n j u g a t e
b a s e
B H + + H 2 O ↔ H 3 O + B +
I o n i z e d
C o n j u g a t e
a c i d
C o n j u g a t e
b a s e
According to Henderson-Hasselbalch equation
for acids pH-pKa = log [ionized/unionised]
for base pH-pKa = log [unionized/ionised]
% ionisation = 100[ 1+10 (pH-pka) ]
When an acid or base is 50% ionised : pH = pKa
Example:The solution of weak acid Aspirin in stomach (pH-1.0) will
get readily absorbed because it is in the un-ionised form(99%).
6. Example: Phenytoin injection must be adjusted to pH 12 with
Sodium Hydroxide to obtain 99.98% of the drug in ionised
form.
Tropicamide eye drops an anti cholinergic drug has a pka of 5.2
and the drug has to be buffered to pH 4 to obtain more than
90% ionisation.
Importance of Ionization of drug
Weak acid at acid pH:
More lipid soluble because it is uncharged, the uncharged form
more readily passes through the biological membranes.
RCOO- + H+ = RCOOH
Weak base at alkaline pH:
More lipid soluble because it is uncharged, the uncharged form
more readily passes through the biological membranes.
RNH3+ = RNH2 + H+
7. 2. Solubility
The solubility of a substance at a given temperature is defined as
the concentration of the dissolved solute, which is in equilibrium
with the solid solute.
Solubility depends on the nature of solute and solvent as well as
temperature , pH & pressure.
The solubility of drug may be expressed in terms of its
affinity/philicity or repulsion/phobicity for either an aqueous or
organic solvent.
The atoms and molecules of all organic substances are held
together by various types of bonds (e.g. hydrogen bond, dipole –
dipole, ionic bond etc.)
These forces are involved in solubility because it is the solvent-
solvent, solute-solute, solvent-solute interactions that governs
solubility.
8. Methods to improve solubility of drugs
1) Structural modification (alter the structure of molecules)
2) Use of Co-solvents (Ethanol, sorbitol,PPG,PEG)
3) Employing surfactants
4) Complexation
Importance of solubility
1. Solubility concept is important to pharmacist because it govern
the preparation of liquid dosage form and the drug must be in
solution before it is absorbed by the body to produce the
biological activity.
2. Drug must be in solution form to interact with receptors.
9. 3. Partition Coefficient
The partition coefficient is defined as the ratio of
unionised drug distribution between organic phase and
aqueous phase at equilibrium. (or)
Partition co-efficient is defined as equilibrium constant
of drug concentration for unionized molecule in two
phases
Partition coefficient (p) (Unionised Drug)
= Conc of Drug in Oragnic phase/ Conc of Drug in Aqueous Phase
Partition co-efficient is one of the Physicochemical parameter which
influencing the drug transport & drug distribution., the way in
whichthe drug reachesthe site ofaction from the site of application.
10. For ionized (acids, bases and salts)
P[Ionized molecule] = [drug]lipid/[1-a ][drug]water
a = degree of ionization in aqueous
solution
Partition coefficient affects the drug transfer
characteristics.
The contribution of each functional group &
structural arrangement help to determine the
lipophilic or hydrophilic character of drug
molecules.
It is widely used in QSAR.
11. Factors affecting Partition Co-efficient
pH
Co solvents
Surfactant
Complexation
Partition Co-efficient are difficult to measure in living system.
They are usually determined in vitro 1-octanol as a lipid phase
and phosphate buffer of pH 7.4 as the aqueous phase.
1-octanol as a lipid phase because,
It has polar and nonpolar region
Po/w is easy to measure
Po/w often correlates with many biological properties
It can be predicted using computational mode
12. The Partition co-efficient, P is dimensionless and its
logarithm, log P is widely used as the measure of
lipophilicity.
The log P is measured by the following methods.
1) Shake flask method
2) Chromatographic method (HPLC)
• Phenobarbitone has a high lipid/water partition
coefficient of 5.9.Thiopentone sodium has a
chloroform/water partition coefficient of about 100,
so it is highly soluble in lipid.
Hence, thiopentone sodium is used as ultra-short
acting barbiturates.
13. What else does lop P affects?
log P B in ding
to
enzymes
/receptor
Aqueous
solubility
Binding to
P450
metabolising
enzymes
Absorbance
through
membrane
Binging to
blood/tissue
proteins
14. Importance of partiti0n coefficient
It is generally used in combination with the Pka to
predict the distribution of drug in biological system.
The factor such as absorption, excretion &
penetration of the CNS may be related to the log P
value of drug.
The drug should be designed with the lowest
possible.
Log P, to reduce toxicity, nonspecific binding &
bioavailability.
15. 4. Hydrogen Bonding
The hydrogen bond is a special dipole-dipole
interaction between the hydrogen atom in a polar
bond such as N-H, O-H or F-H & electronegative atom
O, N, S, F atom.
Dipoles result from unequal sharing of electrons
between atoms within a covalent bond.
These are weak bonds and denoted as dotted
lines.
O-H…….O, HN-H…….O,
The compounds that are capable, of forming
hydrogen bonding is only soluble in water.
Hydrogen bonding is classified into 2 types:
1. Intermolecular
2. Intramolecular
16. 1) Intermolecular hydrogen bonding
It is occur between two or more than two molecules
of the same or different compound.
Due to this increase the boiling point of the
compound & increase the molecular weight of
compound hence more energy is required to
dissociate the molecular for vaporization.
17. 2) Intramolecular Hydrogen bonding
H- bonding occurs within two atoms of the same
molecules.
This type of bonding is known as chelation and
frequently occurs in organic compounds.
Sometimes h-bond develop six or five member rings
due to decrease the boiling point
18. Eg.1) Antipyrin i.e. 1- phenyl 2,3- dimethyl 5- pyrazolone has
analgesic activity.
1-phenyl-3-methyl-5-pyrazolone is inactive.
19. Salicylic acid (O-Hydroxy Benzoic acid)
has antibacterial activity
Para and meta Hydroxy Benzoic acids are inactive
Intermolecular H-bonding of p-isomer enhance water
solubility but decrease in lipid solubility and vice versa for
salyclic acid. Because of lower partition coeffcient, p-isomer
has low antibacterial actitivty.
20. EffectofH-bonding
Allphysical properties affected by H-bonding,
1. Boilingand Melting point
2. Water solubility
3. Strength of acids
4. Spectroscopic properties
5. On surface tension and viscosity
6. Biological products
7. Drug-receptor interaction
21. 5. Proteinbinding
The reversible binding of protein with non-specific and non- functional
site on the bodyprotein without showingany biological effect is
calledasprotein binding.
Protein + drug ⇌ Protein-drugcomplex
Depending on the whether the drug is a weak or strong acid, base or is
neutral, it can bind to single blood proteins to multiple proteins (sereum
albumin,acid-gycoprotienor lipoproteins).
The most significant protein involved in the binding of drug is albumin,
whichcomprisesmore thanhalfof blood proteins.
22. Protein binding values are normally given as the
percentage of total plasma concentration of drug that
is bound to all plasma protein
Free drug(Df)+ Freeprotein(Pf)
Drug/Proteincomplex (Dp)
Total plasma concentration (Dt) = (Df) + (Dp
23. 6. Chelation /Complexation
Complex of drug molecules can’t cross the natural
membrane barriers, they render the drug biological
in-effectivity.
The rate of absorption is proportional to the
concentration of the free drug molecules i.e. the
diffusion of drug.
Due to reversibility of the Complexation,
equillibrium between free drug and drug complex
Drug + complexing agent Drug complex
Complexation reduce the rate of absorption of drug but
not affect the availability of drug
24. Complex results from donor-acceptor mechanism or
Lewis acid base reaction.
Since, Complex drugs cannot cross the membrane,
they reduce the rate of absorption of the drug.
The Compounds that are obtained by donating
electrons to metal ions with the formatiom of ring
structures are called CHELATES.
The compounds that are capable of forming a ring
structure with metal atoms are termed as LIGANDS.
25. Importance of chelates in medicine
a)Antidote for metal poisoning
1. Dimercaprol is a chelating agent – Used in the treatment of
Lead Poisoning
2. Pencillamine is used in the treatment of copper and Wilson
disease.
26. 7. Isosterism
Longmuirintroduced the term isosterismin 1919, which
postulated that two molecules or molecular fragments
containing an identical number and arrangement of
electron should have similar properties and termed as
isosteres.
or
Groups or molecules that impart similar physical,
chemical & biological properties to a molecule due to
similiraties in size, electronegativity or stereochemical
aspects.
27. The purpose of molecular modification is usually to
improve potency, selectivity, duration of action and
reduce toxicit.
Bio-isosteres are substitutents or groups that have
similar physical or chemical properties and hence
similar biological activities patern.
Bio-isosteric replacement may help to decrease
toxicity or to change activity spectra. It may also
alter the metabolic pattern of the drug.
They are classified into two types.,
i) Classical biososteres
ii) Non classical bioisosters.
28. Classical bio-isosteres
They have similarities of shape and electronic
configuration of atoms, groups and molecules which
they replace.
Univalent atoms and groups
i) Cl, Br,I
ii) CH3, NH2, -OH, -SH
Bivalent atoms and groups
i) R-O-R, R-NH-R,
R-S-R,RCH2R
ii) –CONHR, -COOR,
-COSR
Trivalent atomsand groups
i)-CH=, -N= ii) –p=, -AS=
Tetravalentatomsand groups
=c=, =N=, =P=
Ring equivalent
-CH=CH-, -S-,-O-, -NH,-CH2-
29. Application of Classical Bioisosteres in in drug
design
i) Replacementof–NH 2 group by–CH3 group.
Carbutamide
Tolbutamide
R= NH2
R= CH3
ii)Replacementof–OH &-SH
Guanine= -OH
6-Thioguanine= -SH
R SO2 NH CONH(CH2)3CH3
N H
N
N
H 2 N
H N
X
30. Non classicalBioisosteres
Theydo not obeythe stearic andelectronic definition ofclassical
isosteres.
Theydonothave the same number of atoms as a replacement.
Specific characteristics:
1. Electronic properties
2. Physicochemicalproperty of molecule
3. Spatical arrangement
4. Functionalmoiety for biological activity
Examples
Halogens Cl, F,Br,CN
Ether -S-,-O-
Carbonylgroup
Hydroxyl group –OH, -NHSO2R, -CH2OH
Catechol
HO
HO
32. 8. Optical isomerism
Isomers - Same molecular formula
- But Different in their Physical &
Chemical properties
Stereoisomers - Same molecular formula
- But Different arrangement
of atom in Space / Configuration
33. Optical isomerism
Optical isomers differ from each other in their
ability to rotate the plan polarized light.
Dextro-rotatory means which rotate the plan
polarized light to right direction (clockwise), while
which rotate to left side chain is called as Levo-
rotatory.
34. Importance of optical isomerism
Different isomer, it may be possible that one isomer
may be more active than other (or) other may be
having any other activity.
In case of epinephrine, only levo form is active as
compared to dextro because of proper orientation of
the hydroxyl group of the levo epinephrine over the
receptors.
In case of amphitamine, levo amphitamine is having
sympathomimetic activity while dextro amphitamine
is having CNS stimulants.
35. 9. Geometrical Isomerism
These are compounds which differ from each other
in arrangement of atoms or groups around the
double bond.
It can be classified according to the arrangement of
atoms.
CIS form – two similar groups are on the same
side chain
TRANS form – Two similar groups are on
opposite side
36. Importance of Geometrical Isomerism
In case of Diethylstilbesterol, Trans form is 14 times
more active than Cis.
In case of clomiphen is having more anti-esterogenic
activity as compared to the toxoxifen.