Absorption of Drugs

Muhammad Faisal Nadeem

Factors that effect the action of a drug

1.

Rate of accumulation at its site of action

Concentration of the drug at the site of action The duration of the drugs contact at those sites

2.

3.

CELL MEMBRANE
70-100 angstrom units
Trans-cellular absorption Para-cellular absorption

Shabaz & Prasanna; Manipal university, Manipal

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

PASSIVE DIFFUSION

Shabaz & Prasanna; Manipal university, Manipal

1. Passive diffusion

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 the rate of drug absorption from intestine than from stomach. It follows FICKS FIRST LAW of diffusion.
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1. Passive diffusion

FICKS FIRST LAW of diffusion states drug molecule diffuses from a region of higher conc. to the lower conc. until equilibrium is attained.

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dQ/dt: rate of drug diffusion (amt/time) D: diffusion coeff. Of drug through membrane A: surface area of membrane Km/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

 Also called as Convective transport, bulk flow or filtration

LMW, Low mole. size, water soluble drugs

E.g.- Urea, water, sugars

Hmmmm..

Shabaz & Prasanna; Manipal university, Manipal

CARRIER MEDIATED TRANSPORT

CARRIER MEDIATED TRANSPORT

Structure specific
Competition between similar structures Can be explained by Michaelis Menten

equation Cefazolin

FACILITATED DIFFUSION
Carrier mediated transport system operates down the conc. gradient
E.g.- Vit. B12 & IF

ABC proteins
ATP-Binding Cassette Transporters (ABC)
P-glycoprotein (P-gp or MDR1) Multidrug Resistance Associated Proteins

(Mrps) Breast cancer resistant protein (BCRP)

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 tranporter MCA transporter Gabapentin Captopril Foscarnet Pravastatin

IONIC DIFFUSION
Rate of permeation is Unionized mole.> anions > cations

ION PAIR TRANSPORT

Propranolol is a basic drug forms ion pair with Oleic acid
Complexation of Amphotericin B & DSPG

(disteroyl phosphatidyl glycerol)

Endocytosis

Cellular uptake of macromolecular nutrients like Fats, starch, oil soluble vitamins like A, D, E & K and drugs like insulin. It includes two processes: a. Phagocytosis (Cellular uptake of solid particles) b. Pinocytosis (Uptake of fluid solute)

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Summary of Mechanisms

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Solubility
Lipid soluble drugs drugs

that can be dissolved in lipids fatty substances that make up cell membranes including the blood-brain barrier

Water soluble drugs drugs

that can dissolve in water they will not passively move through a cell membrane so they require active transport

Bioavailability
Bioavailability indicates a measurement of the rate and extent (amount) of therapeutically active drug which reaches the general circulation. Absolute bioavailability is 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 bioavailability is a relative amount and relative rate of availability if two formulations (other than i.v.) are compared.

Factors Influencing Drug Absorption And Bioavailability

1. PHARMACEUTICAL FACTORS 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
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1. PHARMACEUTICAL FACTORS 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

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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

slowest TABLETS
Disintegration Dissolution of shell

CAPSULES
ABSORPTION POWDERS SUSPENSIONS EMULSIONS SOLUTIONS

GRANULES
Deaggregation

FINE PARTICLES DISSOLUTION DRUG IN SOLUTION

Biomembrane Absorption

fastest
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INJECTIONS DRUG IN BLOOD