Post on 10-Feb-2018
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Absorption of Drugs
Muhammad Faisal Nadeem
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Factors that effect the action
of a drug 1. Rate of accumulation
at its site of action
2. Concentration of thedrug at the site of action
3. The duration of the
drugs contact at those sites
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CELL MEMBRANE
70-100 angstrom units
Trans-cellular absorption
Para-cellular absorption
Shabaz & Prasanna; Manipal university, Manipal
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Mechanisms of drug
absorption Passive diffusion
Convective transport (Pore transport)
Facilitated diffusion Active transport
Ionic diffusion
Ion-pair transport
Endocytosis
Phagocytosis
Pinocytosis
Shabaz & Prasanna; Manipal university, Manipal
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PASSIVE DIFFUSION
Shabaz & Prasanna; Manipal university, Manipal
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It is called as non-ionic diffusion.Membrane transport of drug and other chemicals
directly through the lipid or aqueous channel is called
passive diffusion.
The rate of drug transfer is directly proportional to the
concentration or electro chemical gradient.
Greater the area and lesser the thickness of the
membrane, faster the diffusion; thus more rapid is therate of drug absorption from intestine than from
stomach.
It follows FICKS FIRST LAW of diffusion.
1. Passive diffusion
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FICKS FIRST LAW of diffusion states drug moleculediffuses from a region of higher conc. to the lowerconc. until equilibrium is attained.
1. Passive diffusion
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dQ/dt: rate of drug
diffusion (amt/time)
D: diffusion coeff. Of drug
through membrane
A: surface area of membraneKm/w: partition coeff. of drug bet. lip. Membrane &
aq. GI fluid
CGIT-C : conc. Diff. in drug in GI fluid and plasma
h: thickness of the membrane
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Also called as Convective transport, bulk flowor filtration
LMW, Low mole. size, water soluble drugs
E.g.- Urea, water, sugars
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Hmmmm..
Shabaz & Prasanna; Manipal university, Manipal
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CARRIER MEDIATED TRANSPORT
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CARRIER MEDIATED TRANSPORT
Structure specific
Competition between similar structures
Can be explained by Michaelis Mentenequation
Cefazolin
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FACILITATED DIFFUSION
Carrier mediated transport system operatesdown the conc. gradient
E.g.- Vit. B12 & IF
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ABC proteins
ATP-Binding Cassette Transporters (ABC)
P-glycoprotein (P-gp or MDR1)
Multidrug Resistance Associated Proteins(Mrps)
Breast cancer resistant protein (BCRP)
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ACTIVE TRANSPORT
Low to high conc.
Energy required
E.g Enalapril small peptide carrier system
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INTESTINE TRANSPORTERS
AA transporter
Oligopeptide transporter
Phosphate tranporterMCA transporter
Gabapentin
Captopril
FoscarnetPravastatin
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IONIC DIFFUSION
Rate of permeation is Unionized mole.>anions > cations
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ION PAIR TRANSPORT
Propranolol is a basic drug forms ion pair withOleic acid
Complexation of Amphotericin B & DSPG(disteroyl phosphatidyl glycerol)
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Endocytosis
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Cellular uptake of macromolecular nutrients likeFats, starch, oil soluble vitamins like A, D, E & Kand drugs like insulin.It includes two processes:
a. Phagocytosis (Cellular uptake of solidparticles)
b. Pinocytosis (Uptake of fluid solute)
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Summary of Mechanisms
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Solubility
Lipid soluble drugs drugsthat can be dissolved inlipids fatty substancesthat make up cellmembranes including the
blood-brain barrier
Water soluble drugs drugsthat can dissolve in water they will not passively move
through a cell membrane sothey require activetransport
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Bi il bilit
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Bioavailability
Bioavailability indicates a measurement of the rate andextent (amount) of therapeutically active drug which
reaches the general circulation.
Absolute bioavailabilityis the absolute fraction of dose
which is available from a drug formulation in general
circulation. It is measured by comparing AUC after i.v.
and extravascular administration.
Relative bioavailabilityis a relative amount and relativerate of availability if two formulations (other than i.v.)
are compared.
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Factors Influencing Drug Absorption And
Bioavailability
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I. Physico-chemical properties of Drug substances
a. Drug solubility and dissolution rate
b. Particle size and effective surface area
(Inversely proportional)
c. Polymorphism & amorphism
d. Salt form of the drug
e. Lipophilicity of drug
f. Drug pKa and pH
g. Drug stability
1. PHARMACEUTICAL FACTORS
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II. Dosage form Related Factors
a. Disintegration time
b. Dissolution time
c. Manufacturing variables
d. Excipients
e. Nature & type of dosage form
f. Product age & storage condition
1. PHARMACEUTICAL FACTORS
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c. Manufacturing variables
i. Method of Granulation
ii Compression Force
d. Excipients
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e. Nature and type of dosage form
TABLETS
ABSORPTIO
N
fastest
GRANULESCAPSULES
SUSPENSIONS
EMULSIONS
SOLUTIONS
INJECTIONS
Disintegration
POWDERS
Dissolution
of shell
FINE PARTICLES
DISSOLUTION
DRUG IN SOLUTION
Biomembrane Absorption
DRUG IN BLOOD
slowest
Deaggregation