Transcript a) Inter molecular hydrogen bonding

PHYSICAL AND CHEMICALPROPERTIES
OF
DRUG MOLECULES
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Introduction:
Definition:
To study the displined preparation of drug product
or substance how to effect the body ,like Distribution,
Metabolisom,Elemenation by involving Physical and
Chemical parameters.
Physical and chemical properties can be influence the
process of drug transported from site of administration
to site of action.
Drug can be produce some Biological response in
the body . It can be Produce response by
interaction with Receptor, Enzymes , Membranes.
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Classification:
Physical &chemical properties of drug molecules
Physical properties
 solubility
 Partition coefficient
Chemical properties
 Hydrogen bonding
 Molar Refractivity
 Complexation
Bio-isosterism
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SOLUBILITY
solubility can be depending up on natureof
solute and solvents well as temperature and pH
K solubility=K SOLUTION
K SOLID
vander wall attraction:
• they are weak inter molecular forces(0.5-1.0 cal/mole)
•Temperature dependent
Dipole-dipole bonding:
•These forces occur when electronegative elements are attracted
to carbon atom
•Stronger(1.0-10cal/mole)
Ionic bonding:
• formation of Ionic bond is attraction of cathion& anions
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 commonly occur in inorganic compounds
• Relatively strong(5kcal/mole)
PARTITION COEFFICIENT
1. Leaving the aqueous extra cellular fluid
2. Passing through a lipid membranes
3. Entering other aqueous environment before
reaching the receptor
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• Partition coefficient is influencing the transport and
distribution
• One of the most widely used properties in QSAR studies
it can be defined as equilibrium constant of drug
concentration for molecules In two phase
p
( unionized mol)=
[drug] lipid
[drug] water
P(ionised mole)=
[drug] lipid
[1-a] [drug] water
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
BULK PROPERTY
Bulk property of the solid form such as
crystalline polymorphism, particle size, powder flow
properties and surface characteristics are likely to
change during process development.
 This can be used in packing of drug substances
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HYDROGEN BONDING
The hydrogen bonding is a special type of dipole-dipole
interaction between the hydrogen atom in a polar bond such as
N-H,O-H,F-H and an electronegative atoms like O,N,F.
eg: H
: O: …………H
:O:
H
H
it can be divided into two types.
a)Inter molecular hydrogen bonding
b) intra molecular hydrogen bonding
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a) Inter molecular hydrogen bonding:

hydrogen bonding occurs between two or more then
molecules of the same or different compounds.

Intermolecular hydrogen bonding increases the boiling
point of the Compound and also its solubility in water.

Dissociation More hydrogen bonding it have more energy
required for evaporation or of the compound
b) Intra molecular hydrogen bonding:
hydrogen bonding occurs within two atoms of the same
molecules.
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•This type of H-bond is commonly known as chelating of
frequently occurs in Organic compounds
•Boiling point , solubility decreases because of formation of
chelating.
•Chelating is not possible in the corresponding meta and Para
position
E.g.; o-nitrophenol
MOLAR REFRACTION
molar refraction is the molar volume corrected by refractive
index
• it represent the size and polarizability of fragment or molecules
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MR = n2-1
n2+1 * MW d
A small MR for the same molecular weight indicates
stronger interaction in the crystal.
BIOISOSTERISM
Langmuir introduced the term isosterism in 1919.
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two molecules (of) ion (of) radical having the same number
and arrangement of electrons are called isosterism
ex:
a) CO & NO2
b) CO2&N2O
 The wide spared application of concept of isosterism
is to modify (or) improve biological activity that has
been rise to the term BIO-ISOSTERISM .
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 Bio-isosteres are substitutes (or) groups that do not
necessary have the same size (or) volume .but have a
similar in chemical (or) physical properties
•It can be divided into two types
1) Classical bio-isoteres
2) Non-classical bio-isosteres
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 Classical bio-isosteres:
 Classical replacement is “like for like “ in terms of number
of atoms , valances, degree of unsaturation aromatic and
then only becomes a bio-isosteric replacement if biological activity is retained
 univalent atom
a) -CH3,NH2
b) –CL, NH2
C)-Br,-I
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• Bivalent atom and group
a) –CH2,-NH,-O
b )COCH2
• Trivalent, tetravalent atoms
non-classical bio-steres:
 The non classical bio isosters comprise group which are
structurally but do not meet the etectronic &steric
requirement in rigorous
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
these isosters retain the activity by mimicking the spatial
arrangement electronic properties (or) physico-chemical
properties of molecules like pka
COMPLEXATION
Complexes (or) co-ordination of compound result from a
donor acceptor mechanism or Lewis acid base reaction.
Any non metallic atom whether free or contained in a neutral
molecule can donate electron that is donor.
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 Compounds able to form ring with metal ion are called
ligands
 Chelating property is restricted to only N, O,S which are
electron donating.
APPLICATIONS:
 Dimer caprol is chelating agent it is an effective
antidote for arsenical lewsite & also used for
antimony, gold& mercury poisoning
 Pencillamine antidote for copper poisioning
 8-hydroxy quinoline -antibactericidal antifungal
by complexing iron or copper
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 IONIZATION OF DRUGS:
 The accumulation of ionised drug in
acomportement of body is known as ion trapping
 The ionisation of drug is dependent on its pka and
the pH.
 Handerson –hassclbatch relation ship gives us
ratio of ionised or non ionised drug
 Non-ionize substances dissolved in lipid
membrane and transported by passive deffusion
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 Ionized drug penetrated slow
IMPORTANCE:
The lower the pH relative to the pKa greater fraction of potentate
drug
Weak acid at acid ph more lipid soluble bcoz it is un charged, the
uncharged form more readily pass through the biological
membrane
Weak base at alkaline PH also follows the same principle
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Compatibility:
 it is the one of the factor for chemical properties
 In can be widely used in preformulation of drugs
 the activity ingredient is reacted with
preservatives, coloring agent ,other substrates
 This properties over come prepare a stable drug
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THANK YOU
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