Physicochemical Properties Sks
Physicochemical Properties Sks
Physicochemical Properties Sks
The main process by which a drug molecule cross the neutral barrier
is,
◦ Simple diffusion
◦ Facilitated diffusion
◦ Pore transport
◦ Diffusion of the ion across the membrane
◦ Active transport
◦ phagocytosis
7
DISTRIBUTION:
Once the drug has been absorbed into the blood ,it
distributed around the body. It get distributed throughout
the blood supply , with in a minute. As the blood
recirculates, the drug moves from the bloodstream into
the body's tissues.
8
Drugs penetrate different tissues at different speeds,
depending on the drug's ability to cross membranes. For
example, the anesthetic thiopental, a highly fat-soluble drug,
rapidly enters the brain, but the antibiotic penicillin, a water-
soluble drug, does not. In general, fat-soluble drugs can cross
cell membranes more quickly than water-soluble drugs can.
10
The resulting metabolites produce the desired therapeutic
effects. Metabolites may be metabolized further instead of
being excreted from the body. The subsequent metabolites
are then excreted . The termination of the drug effect is
caused by bio transformation and excretion .all the
substance in the circulatory system , including
drugs ,metabolites ,and nutrients will pass through the
liver.
11
Storage sites
Plasma proteins, certain tissues, neutral fat, bone and
transcelluar fluids(gastro intestinal tract)are found to act
as a drug reservoirs or storage sites for drugs.
12
The more lipophilic the drug, the more likely it will concentrate in these
pharmacologically inert depots. The ultra short acting, lipophilic
barbiturate thiopental’s concentration rapidly decreases below its
effective concentration following administration. It disappears into tissue
protein, redistributes into body fat, and then slowly diffuses back out of
the tissue depots but in concentrations too low for a pharmacological
response.
13
PROTEIN BINDING:
15
NEUTRAL FAT:
16
Drug Receptor Interactions
RECEPTOR
A macromolecular component of the organism that binds
the drug and initiates its effect.
Ionic interactions
Drug
Receptor Interactions Hydrogen bonding
interactions
Hydrophobic interactions
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.
• Sufficient solubility and membrane permeability is an
important factor for oral absorption.
• The measurement of aqueous solubility depends upon the
following facts.,
1) Buffer & Ionic strength
2) Polymorphism & Purity of the sample
3) pH
4) Super saturation
5) Thermodynamic Vs Kinetic solubility
In ascending homologous series, the Physico chemical
properties like boiling point, viscosity, surface activity and
partition coefficient increases then the aqueous solubility
decreases.
The solubility characteristics of a drug can be increased or
decreased by derivatisation.
1) Structural modification
2) Use of co solvents
3) Employing surfactants
4) Complexation
Partition Co-efficient
Partition co-efficient is one of the Physico chemical
parameter which influencing the drug transport &
drug distribution., the way in which the drug reaches
the site of action from the site of application.
Partition co-efficient is defined as equilibrium
constant of drug concentration for a molecule in two
phases.
P[Unionized molecule] = [drug]lipid
[drug]water
P[Ionized molecule] = [drug]lipid
[1-a ][drug]water
a=degree of ionization in aqueous solution.
Factors affecting Partition Co-efficient
pH
Cosolvents
Surfactant
Complexation
Applications:
R-O-H O R H O H H O H
H O H
H H-O-R
2) Intramolecular Hydrogen bonding
O H
O H
O
O
C
N
OH
O
CH3 N
N
O
H3C
1-phenyl-3-methyl-5-pyrazolone is inactive.
C6H5
HN H
N
O HN
O
H3C
H3C
Salicylic acid(O-Hydroxy Benzoic acid has antebacterial activity
O
H
O
C
OH
O O
OH C HO C
OH OH
CHELATION
As++ As
CHSH + CHS
CH2OH CH2OH
2.Penicillamine
CH3 CH3 CH3
++
H CU H H
CH3 C C COOH CH3 C C COOH CH3 C C COOH
CU
UC
1:1 chelate
NH2 S
1) Riboflavin analogues
The biological activity of riboflavin is due to E =-0.185 volt.
Examples,
1) Riboflavin analogues
The biological activity of riboflavin is due to E =-0.185 volt.
OH
OH
OH
OH
OH OH
OH OH
Cl N N O
N N O
NH
Cl N
NH
O
N
Dichloro riboflavin
O
riboflavin
Riboflavin analogue E0 = -0.095V
Riboflavin E0 = -0.185 V
BH+ H2 O H3O+ B
ionised Conugate Conugate
acid base
Many drugs show stereo selectivity because mostly reeptor binds are
optically active biological macromolecules such as protein, polynuclootide or
glycolipds.
HO
cis-diethylstibesterol
trans-diethylstibesterol Only 7% activity
Estrogenic activity of the trans isomer
Conformational Isomers
Different arrangement of atoms that can be converted
into one another by rotation about single bonds are
called conformations.
- N+ O
I
CH3 CH3
H NHCH3 H NHCH3
H OH HO H
MP = 37-39 MP = 118-120
1 gram/20 mL 1 gram/200 mL
Ephedrine Pseudoephedrine
(Erythro) (Threo)
The category of drugs where the two isomers have
qualitatively similar pharmacological activity but have
different quantitative potencies.
O
O
OH
OH
O O O O
(s)-(-)warfarin (R)-(+)warfarin
Geometric Isomerism
Geometric isomerism is represented by cis/trans isomerism
resulting from restricted rotation due to carbon carbon double
bond or in rigid ring system.
OH
HO OH
HO
cis-diethylstibesterol
trans-diethylstibesterol Only 7% activity
Estrogenic activity of the trans isomer
ISOSTERISM
Longmuir introduced the term isosterism in 1919,
which postulated that two molecules or molecular
fragments containing an identical number and
arrangament of electron should have similar
properties and termed as isosteres.
R SO2 NH CONH(CH2)3CH3
Carbutamide R= NH2
Tolbutamide R= CH3
HN
NH
H2N
Guanine= -OH
N 6-Thioguanine = -SH
N
Non classical Bioisosteres
Carbonyl group S
Catechol
HO
N
HO
N
H
Catechol
A classical e.g. of ring Vs. noncycclic structure is
Diethylstilbosterol & 17-ß oestradiol.
OH
OH
H H
HO
HO
17-ß oestradiol.
trans-diethylstibesterol
REFERENCES:
1.Thomas L . LEMKE , David A . WILLIAMS , Victoria
F.ROCHE,S . William ZITO, Foye’s Principles of
Medicinal Chemistry ,Wolters kluwer Pvt .Ltd, New
Delhi , 6th Edition ,Pg . no. 210 – 298.
59
3. DonaldJ. Abraham ,BURGER’S Medicinal chemistry
Drug Discovery , Wiley inter science publication ,
6th Edition ,Volume -2, Pg. no. 649 – 653.
5. www.wikipedia.com
60
K Y O U
T H A N