A presentation given by a group of students of Faculty of Pharmacy, University of Dhaka, Bangladesh. This presentation discussed with different physiolgical factors of drug absorption, structure of membrane the drug crosses, different transport mechanism etc

1. Physiological Factors
Affecting Drug
Absorption
 Prepared by
1. Sirazum Munira
2. Dilruba Sharmin
3. Ferdowsi Akter
4. Shobnum Alam
5. Amena Ahmed
6. Labony Khondokar

2. What is Absorption?
•Absorption can be defined as the passage of
drug from its site of application into the
systemic circulation
•Absorption is movement of drug into the blood
stream.
Or,

3. Absorption of drug depends on:
• Physicochemical properties of drug
• The nature of drug product
• The anatomy and physiology of the drug
absorption site

4. Physiological Factors Affecting
Drug Absorption
• (1) Routes of drug administration
• (2) Membrane Physiology
i) Nature of cell membrane
ii) Transport processes
• (3) pH and surface area of GIT
• (4) Gastric emptying time
• (5) Gastrointestinal motility
• (6) Splanchnic blood flow
• (7) Drug stability in GIT
• (8) Effect of food and nutrients
• (9) Disease state
• (10) Drug interaction

5. Routes of Administration and
Drug Absorption
• The route of administration (ROA) that is chosen
has a large impact on how fast the drug is taken up
and how much of it arrives at its destination in an
active form.
• The route of administration is determined by the
physical characteristics of the drug, the speed at
which the drug is absorbed, as well as the need to
bypass hepatic metabolism and achieve high conc.
at particular sites.

6. Routes of Administration and
Drug Absorption (cont.)
Oral: Drug is taken orally.
 Features: Absorption takes place along the whole length of
GIT (i.e. large surface area)
 Absorption site: Gastrointestinal epithelia
Buccal/Sublingual: Drug is place in mouth or under tongue.
 Features: Rapid absorption avoiding first-pass effect.
Drugs which are highly lipid-soluble and subject to high
first-pass effect if swallowed are given through this route
(e.g. Nitroglycerine)
 Absorption site: Buccal/ Sublingual mucosa

7. Routes of Administration and
Drug Absorption (cont.)
Inhalation: The drug is inhaled and absorbed through the
lungs
 Features: large surface area and rapid absorption
-Avoids first pass-metabolism.
-Volatile and gaseous drugs are given in this route (e.g
 Absorption site: Alveoli of lung
 Intranasal: drug is given into the nasal cavity
 Absorption site: Nasal membrane
Rectal: Drug is given into rectum e.g. suppositories
 Feature: absorption process avoids first-pass metabolism
 Absorption site: epithelia of rectal wall

8. Routes of Administration and
Drug Absorption (cont.)
Parenteral routes: Biotechnology-derived drugs (e.g. insulin,
erythropoietin, somatotropin) are given through parenteral
route because they are too labile in GIT to be given orally.
Intravenous (IV): placing a drug directly into the blood stream
 Features: no absorption required, 100% bioavailable, rapid
onset of action
Intramuscular (IM): drug injected into skeletal muscle;
absorption is faster then SC but slower than IV
 Absorption site: striated muscle fiber
Subcutaneous (SC): Absorption of drugs from the subcutaneous
tissues
 Absorption site: Subcutaneous tissue

9. Routes of Administration and
Drug Absorption (cont.)
 No single method of drug administration is
ideal for all drugs in all circumstances
 The oral route is the most popular route of
administration of drug because of its-
• Large surface area for absorption
• Compartments with different pH that accommodate
the drugs of different solubility
• Convenient, easy and efficient route compared to
other routes

10. 2. Membrane physiology
•For systemic drug absorption drug molecules must cross
the cell membrane (oral route-intestinal epithelium).
•Drug molecules may pass either
transcellular pathway or paracellular
pathway.
•The permeability of a drug at
the absorption site into systemic
circulation depends on :
-molecular structure and properties of the drug.
-physical and biochemical properties of cell membrane.
•So the biological membranes pose a significant barrier to
drug delivery.

11. i. Structure of cell membrane
• Cell membranes are generally thin,approximately 70
to 100 Å in thickness.
• Composed of primarily of phospholipids in the form
of a bilayer interdispersed with carbohydrates and
protein groups.
• There are several theories as to the structure of cell
membrane such as Danielli-Davson model, Unit
membrane model, Fluid mosaic model.

13. ii. Transport Process
Passage of drugs across cell membranes:
1.Passive diffusion.
2.Carrier mediated transport
• Active transport
• Facilitated diffusion
3.Ion pair formation.
Others are:
- Endocytosis -Exocytosis

14. A. Passive diffusion
• Passive diffusion is the process by which molecules
spontaneously diffuse from a region of higher
concentration to a region of lower concentration.
• It does not require energy.
• Drug molecule diffuses according to Fick’s law of
diffusion:
dQ DAK
dt h
• Passive diffusion is the major absorption processes for
most of the drugs.
)( PGI CC 

15. B. Carrier Mediated Transport
•In carrier mediated transport drug is transported by a
carrier present at the absorption site.
•Numerous specialized carrier mediated
systems are
present in the body especially
in the intestine for the absorption
of ions and nutrients required by
the body.
•It is two types:
-Active transport (energy dependent).
-Facilitated diffusion(not energy dependent).

16. Active Transport
•Active transport requires a carrier molecule and a
form of energy.
The energy is provided by
the hydrolysis of adenosine
tri phosphate.
•Active transport can transport
a drug against a concentration
gradient i.e. from regions of
low drug concentration
to regions of high
drug concentration.

17. Sodium, Potassium, Calcium ions, glucose, amino acids
vitamins like niacin, ascorbic acid are absorbed by this
way.
Drugs like methotrexate (anti cancer drug)-structurally
similar to folic acid, 5-fluorouracil (antineoplastic drug)-
structurally similar to uracil are absorbed by this way.
Only a few drugs are absorbed by active transport
mechanism.

18. Facilitated Diffusion
•Facilitated diffusion also requires a carrier molecule. But
it does not require energy.
•Here the drug moves along
a concentration gradient.
•Some cephalosporin antibiotics
such as cephalexin undergo
facilitated diffusion by an
oligopeptide transporter protein
located in intestinal epithelial cells.

19. C . Ion-Pair Formation
•Ion-pair formation is the main pathway for ionized
drugs specially for which maintain ionized state at any
pH.
•These drugs penetrate the membrane poorly. So the
charged drug forms a complex with oppositely charged
ligand and becomes neutral.
•This neutral complex can easily cross the absorption
barrier by passive diffusion.
Ligand + drug ion-pair absorption barrier drug
+ligand
  
Ex: propranolol forms ion pair with oleic acid.

20. D. Endocytosis
In endocytosis membranes invaginate or pinch in to
form a vesicle enclosed the moving materials inside
the cell.

21. E. Exocytosis
•Exocytosis is the process of a cell exporting material
using vesicular transport.
Intracellular vesicle moves
to the plasma membrane, where
they fuse with the membrane
and release their contents
into surrounding fluids.
•Cells of stomach and pancreatic
cells secrete digestive enzymes
through exocytosis.
•Certain neurotransmitters (such as nor-epinephrine) are
stored in membrane bound vesicles in the nerve
terminal. They are released by exocytosis.

22. pH AND SURFACE AREA OF GIT

23. ORAL CAVITY
• Saliva is the main secretion of the oral cavity
• pH 7
• Contains ptyalin which digests starch.
e.g fentanyl citrate, nitroglycerin etc (lipid
soluble drug)

24. ESOPHAGUS
• It connects the pharynx and the cardiac orifice
of stomach
• pH 5-6
• Very little drug dissolution occurs in it

25. STOMACH
• Fasting pH 2-6
• pH in presence of food is 1.5-2
• Intrinsic factor enhances vit B-12 absorption & gastric
enzymes initiate digestion
• Basic drugs are solubilized rapidly in presence of acid
• pH may be increased due to certain drugs e.g
omeprazole
• Ethanol easily crosses cell membrane & efficiently
absorbed from the stomach
• e.g ibuprofen,aspirin etc absorbed here

26. INTESTINE
• pH 5-8
• Large area for drug absorption
• pH is optimum for enzymatic digestion of protein
and peptide containing food. Hence protein type
drug (e.g insulin) can’t be administered orally
• The influence of absorptive surface area is much
prominent than pH.
• e.g vitamine,diazepam,quinidine etc absorb here

27. COLON AND RECTUM
• pH 5.5-7
• Colon promotes melting of oily drugs to form
emulsion.
• e.gIn crohn’s disease prednisolone,hydrocortisone for
infammatory bowel disease
• Rectums pH is 7 and virtually has no buffer capacity
• Oral SRDF are well absorbed in colon (e.g
theophylline)
• Suppositories are well absorbed in rectum

28. IONIZATION of DRUG
• Acidic drugs are absorbed faster in acidic pH as they remain
unionized in acidic medium of stomach. So they can be
absorbed through lipidic cell membrane.e.g aspirin
,ibuprofen
• Basic drugs are not absorbed well in acidic pH because they
ionized in acidic medium.
• Basic drugs remain unionize in basic medium (small
intestine) and can be easily absorbed.e.g codein
• Acidic drugs ionize in basic medium so can’t be absorbed.
• Highly acidic or basic drug ionize at all pH hence poorly
absorbed in GIT.e.g disodium cromogylate.guanethidine etc

29. GASTRIC EMPTYING TIME
• The time taken for stomach contents to be passed into the
duodenum influenced by gastric motility,activity of pyloric
sphincter etc
• If acidic drugs remain for long time into stomach, they get
absorbed at a faster rate.
• And if basic drug remains for a short time in stomach and
being more time in small intestine, they get easily
absorbed.
• for acidic drug gastric emptying time should be more and
for basic drug less.
• Example: penicillin is unstable in acid and decomposes if
stomach emptying is delayed. Other drugs, such as aspirin,
may irritate the gastric mucosa during prolonged contact.

30. FACTORS INFLUENCING GASTRIC
EMPTYING TIME
Factors Influence on Gastric Emptying
volume The larger the starting volume, the greater the initial rate of
emptying, after this initial period, the larger the original volume,
the slower the rate of emptying.
Type of meal Reduction in rate of emptying to an extent directly dependent
upon concentration of carbohydrate,lipid and protein type food
Osmotic pressure Reduction in rate of emptying to an extent dependent upon
concentration for salts and nonelectrolytes
Physical state of
gastric contents
Solutions or suspensions of small particles empty more rapidly
Body position Rate of emptying is reduced in a patient lying on left side.
Viscosity Rate of emptying is greater for viscous solutions.

31. Contd.
Factors influence on Gastric Emptying
Emotional states Aggressive or stressful emotional states increase stomach
contractions and emptying rate; depression reduces stomach
contraction and emptying.
Disease states Rate of emptying is reduced in some diabetics and in patients
with local pyloric lesions and hypothyroidism; gastric emptying
ratei s increased in hyperthyroidism.
drugs Anticholinergic,narcotic analgesic etc decrease emptying

32. GASTROINTESTINAL MOTILITY
• It tends to move the drug through the
alimentary canal
• This movement helps drug particle to come in
contact with mucosa and absorbed
• The excessively rapid movement of GIT
impairs absorption.

33. Gastrointestinal Motility Disorders
• Achalasia
• Gastroesophageal Reflux Disease (GERD)
• Functional chest pain
• Gastroparesis / Delayed gastric emptying
• Rapid gastric emptying
• Idiopathic vomiting / Cyclic vomiting syndrome
• Functional dyspepsia
• Constipation
• Diarrhoea
• Irritable bowel syndrome
• Fecal incontinence

34. INTESTINAL MOTILITY
• It mix the contents of the duodenum, bringing
them into intimate contact with the mucosal
cells.
• The drug must have a sufficient time at the
absorption site for optimum absorption.
• In case of high motility(e.g diarrhea) the drug
has a very brief residence time and less
opportunity for adequate absorption

35. Factors affecting intestinal motility
a.Physical activity
b.Food
c.Emotional condition
d.Age, gender
e.Disease state,drug etc
It is very important in absorption and bioavalability
of SRDFs,enteric coated dosage forms and drugs
which are absorbed by carrier mediated transport
systems of small intestine.

36. Intestinal Motility Disorders
• Intestinal pseudo-obstruction
• Irritable bowel syndrome
• Fecal incontinence
• Constipation

37. SPLANCHNIC BLOOD FLOW
• Some drugs are achieving higher plasma conc.
after food, this is because food increase
splanchnic blood flow.
• e.g propranolol, chloramphenicol, lithium
carbonate.
• The absorption of some drugs is reduced due to
presence of food (e.g ampicillin, aspirin, L-dopa)
• In hypovalemic state, the splanchnic blood flow is
reduced. So absorption of the drug is also
decreased

38. DRUG STABILITY IN GIT
• Metabolism or degradation by enzymes or
chemical hydrolysis may adversely affect the
drug absorption.
• Destruction in gastric acid (e.g penicillin)

39. EFFECT OF FOOD
• The presence of food in the GI tract affects the
bioavailability of oral drugs.
• Some effects of food on the bioavailability of the oral drugs
include:
• Delay in gastric emptying time
• Stimulation of bile flow
• Change in the pH of GI tract
• Increase in splanchnic blood flow
• Change in luminal metabolism of drug substances
• Physical/chemical interaction of metal with drug substances

40. Contd.
• The nutrient and caloric contents of the meal, meal
volume, meal temperature etc affect drug product
transit time, luminal dissolution, drug permeability
and systemic availability. Thus it affects drug
absorption.
• Absorption of some antibiotics decreases when
administered with food (e.g. penicillin, tetracycline)

41. Contd.
• Absorption of some lipid soluble drugs increases
when administered with food. e.g. metazalone.
• The presence of food in the GI lumen stimulates the
flow of bile which increases the solubility of fat
soluble drugs by forming micelle.
• The presence of food in the stomach lowers the pH
which causes rapid dissolution and absorption of
basic drugs with limited aqueous solubility. e.g.
cinnarizine

42. Contd.
• Drugs irritating to GI mucosa (e.g: erythromycin,
aspirin, NSAIDs etc) given with food to reduce the
irritation by decreasing the rate of drug absorption.
• In the presence of food, enteric coated and non
disintegrating drug products can not reach the
duodenum rapidly, thus they delay drug release &
systemic drug absorption.

43. Contd.
• Food can also affect the integrity of dosage form
which causes an alteration in the release rate of the
drug. e.g. theophylline.
• Timing of drug administration is important as taking
a medication either 1 hr before or 2 hr after meals ,
avoid any delay in drug absorption.

44. Effect of nutrients on drug absorption
• Absorption of water soluble vitamins (e.g. B-
12, folic acid) in the stomach are facilitated by
forming complex with intrinsic factors.
• Absorption of calcium in the duodenum is
facilitated by vita-D by increasing calcium
binding protein which binds calcium in the
intestinal cell & transfer it to the blood
circulation.

45. Contd.
• Grape juice contains various flavonoids e.g.
naringin which inhibits cytochrome P-450
enzymes . Thus it inhibits absorption of some
drugs.

46. EFFECT OF DISEASE STATES
• Drug absorption differs in any disease which causes
changes in –
• 1. Intestinal blood flow
• 2.Gastrointestinal motility
• 3.Changes in stomach emptying time
• 4.Gastric Ph
• 5.Intestinal pH
• 6. Permeability of gut wall
• 7. Bile secretion
• 8.Digestive enzyme secretion
• 9.Alteration of normal GI flora

47. Contd.
• Patient with Parkinson’s disease have difficulty
swallowing & greatly diminished GI motility
• Patient on tricyclic antidepressants &
antipsychotic drugs reduce GI motility which
delay drug absorption
• In achlorhydric patient weak-base drugs
remain undissolved in stomach because no
adequate acid e.g. Dapsone

48. Contd.
• In patient with acid reflux disorder ,PPI such as
omeprazole , render stomach achlorhydric, may
affect drug absorption
• HIV-AIDS patients are prone to a number of GI
disturbances e.g. increased gastric transit time,
diarrhea
• CHF patient with persistent edema reduce blood
flow to the intestine & intestinal motility results
in decrease absorption e.g. furosemide

49. Contd.
• Crohn’s disease causes impaired absorption
due to reduce surface area & thicker gut wall
e.g. higher plasma propranolol conc. observe
in crohn’s disease
• Patient with Celiac disease increase rate of
stomach emptying & permeability of small
intestine
• Cephalexin absorption increase in Celiac
disease

50. DRUGS THAT AFFECT
ABSORPTION OF OTHER DRUGS
• Metoclopramide stimulates stomach contrac
tion & increases intestinal peristals
• Decrease the peak drug conc. by reducing
effective time for absorption
• For example, digoxin absorption is reduced by
metoclopramide but increased by
propantheline bromide

51. Contd.
• Anticholinergic drug (propantheline bromide)
may slow stomach emptying &motility of
small intestine
• Tricyclic antidepressants & phenothiazines
with anticholinergic side effects cause slower
peristalsis & stomach emptying may delay in
drug absorption
• Antacid not given with cimetidine,tetracycline
because reduce absorption

52. Contd.
• PPI e.g. omeprazole raise gastric pH
• Interfere with drugs for which gastric pH
affects bioavailability (e.g.ampicillin)& enteric-
coated drug product (e.g. aspirin)
• Cholestyramine is a nonabsorbable ion-
exchange resin for the treatment of
hyperlipemia
• It binds warfarin,thyroxine,thereby reducing
absorption of these drugs.

53. Contd.
• Erythromycin inhibits the hepatic metabolism
of a number of drugs e.g. Digoxin.
• Antibiotic eliminates a species of intestinal
flora that inactivates digoxin,thus leading to
greater reabsorption of drug from the
enterohepatic circulation.

54. THANK YOU