absorption of drugs.ppt

7/22/2019 ABSORPTION OF DRUGS.ppt

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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



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PASSIVE DIFFUSION



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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..



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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

absorption of drugs.ppt

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