ppt for RTMNU students

1. ABSORPTION OF DRUGS
By
Mr. Harshad Govind Salpe
Guide
Dr. N. J. Duragkar
Sharad Pawar College of Pharmacy
Wanadongri, Hingna Road,
Nagpur-441 110 [M.S.]
2013-2014

2. DEFINATION
Drug absorption is defined as the process of movement of
uncharged drug from the site of administration to the systemic
circulation.
Absorption can also be defined as the process of movement
of uncharged drug from the site of administration to the site
of measurement i.e. plasma

3. Route of absorption
The Enteral
Route
The Parenteral
Route
The Topical
Route

4. GASTROINTESTINAL ABSORPTION OF DRUG
Movement of drug across the one or more biological
membrane is called as drug transport.

5. CELL MEMBRANE STRUCTRE AND
PHYSIOLOGY
• Double layer of
amphiphilic phospholipid
molecules
• Hydrophobic core
• Hydrophilic head
• Mayonnaise sandwich
• Aqueous filled pores or
perforations of 4-10 A0 in
diameter present

6. MECHANISMS OF DRUG ABSORPTION
•Passive diffusion
•Pore transport
•Facilitated diffusion
•Active transport
•Ion or electrochemical diffusion
•Ion-pair transport
•Endocytosis

7. PASSIVE DIFFUSION
•Non ionic diffusion
•No energy source required
•Process for >90% of the drug
•Based on Fick’s law
•Driving force – concentration or
electrochemical gradient

8. Fick’s law
D
rug molecule diffuse from a region of higher concentration to one of lower
concentration until equilibrium is attained and that the rate of diffusion is directly
proportional to the concentration gradient across the membrane.
dQ/dt = DAKm/w (CGIT – C)
h

10. PORE TRANSPORT
•Also called as convective
transport, bulk flow or filtration
•No energy source required
•Process for low molecular weight,
low molecular size & water soluble
drug
•Molecular weight upto 400
daltons be absobed
•Ex- sugar, water, urea
•Driving force – hydrostatic
pressure or osmotic differences
across membrane
•Importance for renal excretion

11. CARRIER-MEDIATED
TRANSPORT
•Carriers may be enzyme or some other component of the
membrane
•Carriers binds reversibly or noncovalently with solute
molecules
•Ex- monosaccharides, amino acids & vitamines

12. IMPORTANT CHARACTERISTICS
•Structure specificity
•Drug having Structure similar to essential nutrients called false nutrients
•Ex- Antineoplastic agents like 5-fluorouracil & 5-bromouracil
•No. of carrier limited – competition between agents having similar
structure
•System is capacity limited
•Mixed order kinetics also called Michaelis-Menten, saturation or non
linear kinetics
Passive diffusion
•Site specific (absorption window)
Concentration of drug at the absorption site
Rate of drug absorption
Carrier-mediated transport

13. FACILITATED DIFFUSION
•Carrier mediated transport system
that operates Down the
concentration gradient (Downhill
transport)
•Faster than simple passive
diffusion
•Driving force- Concentration
gradient
•No energy expenditure is involved
•Ex- entry of glucose in RBC &
intestinal absorption of Vitamins
B1 & B2

14. ACTIVE TRANSPORT
•More important process than facilitated diffusion.
•Against the concentration gradient or uphill transport
•energy is required
•As the process requires expenditure of energy, it can
be inhibited by metabolic poisons that interfere with
energy production
•A few lipid-insoluble drugs that resemble natural
physiologic metabolites E.g. 5-fluorouracil are
absorbed from the gastrointestinal tract by this process
•Endogenous substance that are transported – sodium,
potassium, calcium, iron, glucose, certain amino acid
& vitamins like niacin, pyridoxin, ascorbic acid

15. IONIC OR
ELECTROCHEMICAL
DIFFUSION
•Charge on membrane influences permeation of drugs
•Order of permeation – unionized molecule > anions > cations
•Driving force – potential deference or electrical gradient

16. ION-PAIR TRANSPORT
•Quaternary ammonium ion compounds & sulfonic acid
ionized under all pH conditions
•Endogenous ion – mucin
Membrane
Passive diffusion
_
_ _ +
GI lumen Blood
+
+
Cationic
drug
Endogenous
anion
Neutral ion-pair
complex Free drug

17. ENDOCYTOSIS
• Engulfing extracellular material
• Responsible for the uptake of
macromolecular nutrients like fats &
starch, oil soluble vitamins like A, D, E, K
and drug such as linsulin
• In endocytosis, there are three process:
A) Phagocytosis
B) Pinocytosis
C) Transcytosis

18. Phagocytosis
(cell eating) adsorptive uptake of solid particulates

19. Pinocytosis
(cell drinking) uptake of fluid solute
This process is important in the absorption of
oil soluble vitamins & in the uptake of
nutrients.

20. Transcytosis
It is a phenomenon in which endocytic vesicle is transferred
from one extracellular compartment to another.

21. FACTORS INFLUENCING DRUG ABSORPTION AND
BIOAVALILABILITY
BIOPHARMACEUTICAL CONSIDERATIONS IN
DOSAGE FORM DESIGN
THE PROCESS CONSISTS OF FOUR STEPS
•Disintegration of the drug product
•Disaggregation and subsequent release of the drug
•Dissolution of drug in the aqueous fluids at absorption site
•Movement of the dissolve drug through the GI membrane into the systemic
circulation and away from absorption site
Slowest step is called rate-determining or rate-limiting
step (RDS)

22. FACTORS AFFECTING DRUG ABSORPTION
A PHARMACEUTICAL FACTORS
1. Physiochemical properties of drug substances
• Drug solubility and dissolution rate
• Particle size and effective surface area
• Polymorphism and amorphism
• Pseudopolymorphism (hydrates/solvates)
• Salt form of drug
• Lipophilicity of drug
• pKa of the drug and pH
• Drug stability
2. Dosage form and characteristics and pharmaceutic ingredients
• Disintegration time
• Dissolution time
• Manufacturing variables
• pharmaceutic ingredients (excipients/ adjuvants)
• Nature and type of dosage form
• Product age and storage conditions

23. FACTORS AFFECTING DRUG ABSORPTION
A PATIENT RELATED FACTORS
1. Age
2. Gastric emptying time
3. Intestinal transit time
4. GI pH
5. Disease state
6. Blood flow trough GIT
7. GI contents
• Other drug
• Food
• Fluids
• Other GI contents
8. Presystemic metabolism by
• Luminal enzymes
• Gut wall enzymes
• Bacterial enzymes
• Hepatic enzymes

24. PHYSIOCHEMICAL FACTORS AFFECTING DRUG
ABSORPTION
Drug solubility and dissolution rate
The rate determining steps in absorption of orally administered
drugs are:
1. Rate of dissolution
2. Rate of drug permeation through the biomembrane.
Dissolution is rate determining step for hydrophobic & poorly
aqueous soluble drugs.
E.g. Griesiofulvin & Spironolactone.
Permeation is the rate determining step for hydrophilic & high
aqueous soluble drugs.
E.g. cromolyn sodium OR Neomycin.

25. Solid
dosage
form
Solid
drug
particles
Drug in
solution at
absorption
site
Drug in the
body