The document discusses various factors that affect oral drug absorption, including biological, physiological, physico-chemical, and pharmaceutical factors. It provides details on several biological factors such as penetration of drugs through the gastrointestinal tract, blood brain barrier, placental barrier, skin, eyes, and mucous membranes. It also examines physiological factors like patient factors, gastrointestinal physiology, pH of the gastrointestinal tract, presystemic metabolism, absorption sites, protein binding, gastrointestinal transit time, and circadian rhythms that influence oral drug absorption. The document is presented by Deepak Kumar and provides a comprehensive overview of the key factors involved in oral drug absorption.

1. Factors Affecting Oral
Absorption
1. Biological factors
2. Physiological factors
3. Physico-chemical factors
4. Pharmaceutical factors
By
Deepak Kumar, M-Pharm(AACP)
(Pharmaceutics).

2. Biological Factors:-
a. Penetration of drugs through the GIT.
b. Penetration of drug through the blood brain
barrier.
c. Penetration of drug through the placental
barrier.
d. Penetration of drug through the skin.
e. Penetration of the drug through the eyes.
f. Penetration of drugs from the mucous
membrane.

3. Overall picture of drug absorption,
distribution, and elimination

4. a)Penetration of drug through the GIT:-
1.The GI mucosa,is a semipermeable membrane,across which transport of
various nutrients as well as substances foreign to the body takes place.
2.These compounds are normally absorbed across this membrane into the
blood by- Passive diffusion
Active diffusion
Pore transport
Pinocytosis,etc
b)Penetration of drug through the blood brain barrier:-
1. BBB is a sheath of endothelial cells lining the capillaries.
2. Penetration of drugs depends on-size of molecules,lipid solubility.
3. Highly lipid soluble drugs like thiopental,reach the brain very soon.
4. Rate of penetration is proportional to the size of the molecule.
ex-Insulin penetrates slowly,urea penetrate rapidly.

5. Blood brain barrier:-

6. Example:-

7. c)Penetration of drug through the placental barrier:-
1.Placenta is the membrane separating foetal blood from the maternal
blood.
2.Passage of drugs occur by -simple diffusion
-Active transport
-Pinocytosis
-Filtration
Examples,of drugs of moderate to high lipid solubility are sulphonamides,
barbiturates,anticonvulsants,narcotic analgesics,antibiotics & steroids.
Placental Barrier

8. d)Penetration of drugs across the skin:-
A) Through epidermis(Trans-epithelial absorption)
Layers of epidermis:-
-Basal layer
-Prickle cell layer
-Granular layer
-Horny layer / stratum corneum

9. =Absorption of a drug is proportional to be lipid solubility,since the epidermis
behaves as a lipid barrier,the mechanism of absorption being passive
diffusion.
=Absorption through skin could be enhanced by:-
1)Innuction
2)Iontophoresis
3)Sonophoresis
4)Magnetophoresis.
1)Innuction-It involves suspending the drug in an oilly vehicle and rubbing
the resulting preparation on the axis.
2)Iontophoresis- Transfer of drugs that ionize
|
Transfering of positively charged drug across the skin,an anode is placed in
contact with the drug dissolution
|voltage is applied
+vely charged drugs repell from anode
|
Penetrates through the skinSystemic circulation

10. B) Via the hair follicles (Pilosebaceous absorption)
Factors affecting percutaneous absorption:-
1)Thickness of horny layer - The horny layer is thickest on the palms and
soles and thinnest on the face.
2)Skin condition - Permeability of the skin is affected by age,disease
state,climate and injury.
3)Hydration of skin - Hydration of the skin by use of wetting agent or
occlusion promotes drug absorption.
4)Skin temperature - The permeability of drugs increases with increase in
skin temperature.
5)Chemical form of the drug and the vehicle - Fluocinolone acetonide
which when used topically is over 100 times as
active as hydrocortisone and is useful for treating
psoriasis.
6)Incorporation of permeation enhancers - Dimethyl sulphoxide,a surfectant
which is miscible with water as well as organic
solvents enhances percutaneous absorption of
3)Sonophoresis- This makes use of sound waves to enhance the penetration.
4)Magnetophoresis- It involves the application of magnetic field and
enhancing
the absorption of drugs.

11. e)Penetration across the eyes :-
->The cornea,lens and vitreous body of the eye are all transparent media
with no blood vessels . Oxygen and nutrients are transported to these
non vascular tissues by the aqueous humour which has a high oxygen
tension and same osmotic pressure as blood.
->The intraocular bioavailability of topically applied drugs is extremely poor
due to - presence of lachrymal fluids in the cul-de-sac
- nasolacrimal drainage
- interaction of drugs by other substances
->Penetration depends upon the polarity
of the vehicle
Ex-Absorption of dexamethasone from
acetate buffer is faster than from
phosphate buffer which is more polar.

12. f)Penetration through the mucous membrane:-

13. ->The mucous membrane is generally highly vascular in nature.The
barrier for drug absorption is the capillary endothelial cell membrane
which is lipoidal and consists of pores.Thus,lipid soluble drugs can
easily penetrate by the process of diffusion and small drug
molecules can penetrate by pore transport.

14. REFERENCES:-
Textbook of BIOPHARMACEUTICS &
PHARMACOKINETICS(Dr.Shobha Rani).
BIOPHARMACEUTICS &
PHARMACOKINETICS(F.V.Manvi,
K.Nanjwade,K.Patel)
Physiological Factors Affecting Oral
Absorption.Article by- A. S. Adebayo,
Ph.D
Kulkarni

15. Questions:-
1.Discuss in detail the biological factors of
drug absorption?(10,20 Marks)
2.With the help of a neat labelled diagram
explain the Blood Brain Barrier?(10 Marks)
3.How can the penetration of the drugs
through the skin can be enhanced?(5
Marks)
4.What factors affect absorption of drugs
through the skin?(5 Marks)

16. ***END OF PRESENTATION***
THANK YOU

17. Physiological Factors:-
a. Patient factors
b. Gastrointestinal physiology
c. pH of Gastrointestinal tract
d. Presystemic Metabolism
e. Absorption sites
f. Protein Binding
g. Gastrointestinal Transit
h. Circadium Rhythm

18. 1)Age:- Absorption,distribution,metabolism and elimination decline with age.
On the otherhand young children may not absorb some drugs as
systems are not developed.
2)Sex:- In pregnancy the total body water increases(6-8 L);secondly variations
in hormones,weight distribution may have direct or indirect effect on
drug distribution.During the luteal phase of the menstrual cycle and
during pregnancy when progesterone levels are high there is a delay in
GI transit.
3)Body weight:- Whether the body weight is lean body mass or fat mass
significantly affects drug distribution.Patient with smaller volumes of body
fluids and of lighter weight usually have higher blood drug levels.
4)Activity and Posture:- The activity and posture dependent changes in plasma
volume or blood flow rate may show variation in pharmacokinetics of
certain drugs.
.
a)Patient Factors:-

19. Continued:-
5)Food:- Absorption is maximum from the empty stomach.Food reduces
rate of absorption of drug but doesnot changes the extent of
absorption.
ex-Aspirin,acetaminophen,phenobarbital sodium and rifampin.
In fasted state the volume of fluid is low.So,a meal can rise ph to 3-
Milk to-6.
6)Medicines:- Any drug that influences the rate of gastric emptying can
change drug absorption.The increase in gastric pH may increase
the solubility of acidic drugs and decrease the solubility of basic
drugs.
7)Disease conditions:- GI secretions and GI transit differ during different
disease like-GI ulcer,acidity,diarrhoea,constipation. Aspirin and
paracetamol have good absorption from small intenstine

20. b)Gastrointestinal physiology:-
Characteristics of G.I physiology :-
pH Membrane Blood Supply Surface Area Transit Time By-pass liver
BUCCAL approx 7 Thin Good, fast
absorption
with low
dose
small Short unless
controlled
Yes
ESOPHAGUS 5 - 6 Very thick, no
absorption
- small Short -
STOMACH 1 - 3 Normal good small 30 - 40 minutes,
reduced
absorption
no
DUODENUM 6 - 6.5 Normal good very large very short (6"
long),
window
effect
no
SMALL
INTESTINE
7 – 8 Normal good very large 10 -
14 ft, 80
cm 2
/cm
about 3 hours no
LARGE
INTESTINE
5.5 - 7 - good not very large 4 -
5 ft
long, up to 24 hr lower colon

21. Gastrointestinal Physiology:-

22. c)Gastrointestinal pH:-
Average pH values at different locations in GIT:-
GI fluid pH influence drug absorption in a several ways:-
1.Disintegration-With enteric coated formulations,the coat dissolves in the
intestine followed by disintegration of the tablet.
2.Dissolution- A pH that favours formation of salts of the drug enhances the
dissolution.
3.Absorption- Depending upon the drug pKa and whether it is an acidic or
basic drug the GI pH influence drug absorption by determining the
amount of drug that would exist in unionized form at the site of
absorption.
4.Stability- Stomach pH->Acidic->Degradation of penicillinG & erythromycin
Location Average pH in fasted stage Average pH in the fed state
1.Stomach 1.3 4.9
2.Duodenum 6.5 5.5
3.Jejunum 6.6 5.2-6.0
4.Ileum 7.4 7.5

23. d)Presystemic Metabolism:-
For drugs administered orally,two main reasons for its decreased
bio-availability are- 1.Decreased absorption
2.Pre-systemic metabolism/First-pass effect.

24. ->Presystemic metabolism of drug can occur in GIT or in membrane.
->The loss of drug through biotransformation by such eliminating organs during
its passage to systemic circulation is called as first
pass/pre-systemic metabolism.
->The four primary systems which affect pre-systemic metabolism of the drug
are:-
1.Luminal enzymes
2.Gut wall enzymes/mucosal enzymes
3.Bacterial enzymes
4.Hepatic enzymes
->If a drug is subject to rapid metabolism in liver,then a reduced absorbed dose
reaches in blood circulation.

25. e)Absorption sites:-
Drugs are having a particular site for maximum absorption.The following table
summarizes the comparative drug absorption from different regions of GI
tract.
Drug Stomach Jejunum Ileum Colon
Furosemide **** - ** *
Isradipine ** ** **** ****
Nifedipine ** ** - ****
Omeprazole - * ** ***
Phenytoin - * ** ***
Theophylline *** ** - **

26. f)Protein binding:-
->The drug bound to the proteins in blood(plasma),membranes or tissues
is difficult to diffuse,absorb,reach to the site of action and interact with
receptors.
->The rate of biotransformation and elimination are also decreased
because of protein binding.
->The protein binding is usually reversible and it releases drug from the
protein until drug in the extravascular water equilibrates with free drug
in the plasma.
->Binding may be competitive where one drug displaces another drug,eg-
aspirin dispalces penicilin.
->Infants and adults show difference in plasma protein binding and tissue
binding of drugs,eg- Local Anesthetics
Sulfaphenazole
-> Albumin is the main component ,which binds to a wide variety of drugs.

27. g)Gastrointestinal Transit:-
->Apart from dissolution of drug and its penetration through the biomembrane,
passage from stomach to small intestine called as gastric emptying.
->Rapid gastric emptying is advisable where,
1) Rapid onset of action is desired.
2) Dissolution of drugs require in the intestine.
3) The drugs are not stable in gastric fluids.ex-penicillinG and erythromycin.
4) The drug is best absorbed from the distal part of the small intestine.
->Delayed gastric emptying is recommended in particular where,
1)Food promotes drug dissolution and absorption. ex-Griseofulvin.
2)Disintegration and dissolution of dosage form is promoted by gastric
fluids.
3)The drugs dissolve slowly. ex-Griseofulvin.
4)The drug irritating gastric mucosa. ex-aspirin,nitrofurantoin.
5)The drugs are absorbed from the proximal part of the small intestine and
prolong drug absorption site contact is desired.ex-vit-B12,C.

28. Factors Affecting Gastric Emptying :-
Volume of Ingested Material As volume increases initially an increase
then a decrease. Bulky material tends to
empty more slowly than liquids
Type of Meal
Fatty food Decrease
Carbohydrate Decrease
Temperature of Food Increase in temperature, increase in
emptying rate
Body Position Lying on the left side decreases
emptying rate. Standing versus lying
(delayed)
Drugs
Anticholinergics (e.g. atropine) Decrease
Narcotic (e.g. morphine) Decrease
Analgesic (e.g. aspirin) Decrease

29. Parameters used to quantify gastric emptying:-
1)Gastric emptying rate:- Speed at which the stomach contents move into
intestine.
2)Gastric emptying time:- It is the time required for the gastric content to empty
into the intestine.
3)Gastric emptying:- It is the time taken for half the stomach to emptying
Drugs affecting Gastric Emptying time:-
Decrease gastric emptying rate Increase gastric emptying rate
Antihistamines Anticholinesterases
Antimuscarenic drugs -Atropine,Propantheline -Neostigmine
-Phyostigmine
Ganglion blocking drugs Dopamine antagonists
- Hexamethonium - Domperidone
Opiod analgesics - Metoclopramide
- Diamorphine,Morphine Iproniazid
Reserpine
Sodium bicarbonate
Phenothiazines
Sympathomimetics
- Isoprenaline


30. h)Circadium Rhythm:-
-> The functions of body including body secretions and pharmacokinetics display its
own time schedule per day and over entire life period,called as circadium rhythm.
->Diseases such as bronchitis,ischemic heart attacks,allergic conditions(asthma
attack),rheumatoid arthritis display circadium dependent symptoms in early morning
hours
->Acidity gradually increases from 4pm and it is max at midnight.Patients suffering
from sleeping disorders need second dose at around 2am.
->NSAID,theophylline,nifedipine,oral nitrates and propranolol have been reported to
have higher Cmax and shorter Tmax when administered in the morning than evening.
->It was correlated with the faster gastric emptying which carry drug to efficient
absorption sites of small intestine .

31. REFERENCES:-
Textbook of BIOPHARMACEUTICS &
PHARMACOKINETICS(Dr.Shobha Rani).
BIOPHARMACEUTICS &
PHARMACOKINETICS(F.V.Manvi,
K.Nanjwade,K.Patel)
Physiological Factors Affecting Oral
Absorption.Article by- A. S. Adebayo,
Ph.D
Kulkarni

32. Questions:-
1.Discuss in detail the physiological factors
of drug absorption?(10,20 Marks)
2.What is gastric emptying?In which
condition rapid and delayed gastric
emptying is advisable?(10 Marks)

33. ***END OF PRESENTATION***
THANK YOU