The document provides information about drug absorption. It defines drug absorption and discusses the processes that determine absorption such as passive transport, active transport, endocytosis, and transcytosis. It describes factors that affect drug absorption such as molecular size, degree of ionization, physical form, chemical nature, concentration, dosage forms, pH, and other substances in the gastrointestinal tract. The key points are that drug absorption involves movement of the drug into the bloodstream and is determined by the drug's properties and route of administration.

1. PHARMACEUTICAL CHEMISTRY
PRESENTED BY: GROUP NO. 4
• KANIZ FATIMA
• FATIMA HAYAT
• SHAZIA NASIM
• SYEDA MAIRA HAMID
• SHERBANO
• SMAIRA AFZAL
• TUBA ALVI
PRESENTED TO: Dr. SOBIA
TOPIC: DRUG ABSORPTION
DATE: 4TH MAY, 2015

2. WHAT IS DRUG?
Drug is any chemical or biologic substance that affects
the body and its processes.
OR
A substance used as medication or in the preparation of
medication.
Its MOL.WT should be less than 500.

3. PHARMACOKINETICS
It describes how the body handles a drug and
accounts for the process of:
•Absorption
•Distribution
•Metabolism
•Excretion

5. DRUG ABSORPTION
•Drug absorption is the movement of a drug
into the bloodstream after administration.
•Absorption affects bioavailability____
•How quickly and how much of a drug reaches
its target of action.

6. Drug absorption is determined by:
1) Drug’s physicochemical properties
2) Formulation
3) Route of administration(oral, buccal, inhalation,
parenteral, topical).
Regardless the route, drug must be in solution to
be absorbed.

7. BIOLOGICAL MEMBRANE
Biological membranes consist of a lipid bilayer
separating different compartments, with protein
molecules acting as enzymes, channels or carrier
proteins.
Drugs have to cross the biological membranes to
get absorbed.

8. RULE OF FIVE
The medicinal chemist Christopher Lipinski and his
colleagues analysed the physico-chemical properties of
more than 2,000 drugs, and concluded that a compound is
more likely to be membrane permeable and easily
absorbed by the body if it matches the following criteria:
•Molecular weight of drug should be less than 500.
•Less than 5 hydrogen bond donor.
•Less than 10 hydrogen bond acceptor.
•Pka value should be less than 5.

9. PROCESSES DETERMINING ABSORPTION
•PASSIVE TRANSPORT
•ACTIVE TRANSPORT
•ENDOCYTOSIS
•TRANSCYTOSIS
•ORAL ADMINISTRATION
•PARENTERAL ADMINISTRATION
•PORE TRANSPORT
•ION PAIR TRANSPORT

10. PASSIVE TRANSPORT
PASSIVE TRANSPORT IS A MOVEMENT OF BIOCHEMICAL AND
OTHER ATOMIC OR MOLECULAR SUBSTANCES ACROSS CELL
MEMBRANES. SO THE DRUG CAN CROSS CELL MEMBRANES
USING PASSIVE TRANSPORT IN THREE WAYS :
• SIMPLE DIFFUSION
• FILTRATION/ AQUEOUS DIFFUSION
• BULK FLOW

11. SIMPLE DIFFUSION
• MOST OF THE DRUGS ARE ABSORBED BY SIMPLE DIFFUSION, WHICH IS THE
MOVEMENT OF MOLECULES DOWN THE CONCENTRATION GRADIENT I.E. FROM
HIGHER CONCENTRATION (GI FLUIDS) TO LOWER CONCENTRATION (BLOOD).
• THIS TYPE OF TRANSPORT OCCURS MOSTLY FOR THE LIPID SOLUBLE DRUGS.
• DIFFUSION RATE IS DIRECTLY PROPORTIONAL TO THE GRADIENT BUT ALSO
DEPENDS ON THE MOLECULE’S LIPID SOLUBILITY, SIZE, DEGREE OF
IONIZATION, AND THE AREA OF ABSORPTIVE SURFACE.
NON-SPECIFIC:
• THIS TYPE OF TRANSPORT IS NON-SPECIFIC I.E. NO CARRIER PROTEINS ARE
REQUIRED.
ENERGY EXPENDITURE:
• NO ENERGY IS REQUIRED FOR THIS TYPE OF TRANSPORT.

12. FILTRATION
• FILTRATION INVOLVES THE AQUEOUS CHANNELS OR PORES
THROUGH WHICH HYDROPHILIC DRUGS CAN PASS.
• FILTRATION OCCURS IN THE JEJUNUM AND PROXIMAL TUBULES
OF KIDNEYS.
• IT IS ABSENT IN THE STOMACH AND THE LINING OF THE URINARY
BLADDER.
• ONLY CERTAIN IONS LIKE NA+ AND DRUGS OF LOW MOLECULAR
WEIGHT, LIKE ETHANOL AND GLYCEROL CAN UNDERGO
FILTRATION.

13. BULK FLOW
• THE DRUG IN THIS PROCESS PASSES THROUGH THE PORES BETWEEN
CAPILLARY ENDOTHELIAL CELLS.
• THE PASSAGE IS INDEPENDENT OF WATER AND LIPID SOLUBILITY.
• BULK FLOW IS THE PHENOMENON MOSTLY SEEN WITH THE INTRA
MUSCULAR AND SUBCUTANEOUS INJECTIONS. DRUG IS INJECTED IN
BULK FORM INTO THE MUSCLE. DRUG MOLECULES ALONG WITH THE
AQUEOUS MEDIUM PASS THROUGH THE PORES OF ENDOTHELIUM, AND
DIFFUSE INTO THE BLOOD.
• BULK FLOW DOES NOT OCCUR IN BRAIN BECAUSE OF ABSENCE OF
PORES.
• BULK FLOW IS DEPENDENT ON THE BLOOD FLOW, MORE THE BLOOD
FLOW, MORE RAPID IS THE ABSORPTION. THIS IS WHY THE AREA IS
RUBBED AFTER INTRA MUSCULAR INJECTIONS TO INCREASE THE

14. ACTIVE MEMBRANE TRANSPORT
Active membrane transport is for the drugs which
cannot cross the lipid membrane and require
transport proteins.
It involves the penetration of the drug molecule in
the lipid bilayer membrane from lower
concentration to the higher concentration of
solutes against the concentration gradient
• with the expenditure of energy and
• with the help of special transport protein.

15. “
”

16. FEATURES OF ACTIVE TRANSPORT
•Relatively unusual
•Selective
•Saturable
•Requires Energy Expenditure in the form of ATP
•Limited to drugs structurally similar to endogenous
substances e.g: ions, vitamins, sugars, amino acids
•Uptake of Levo Dopa by brain which utilize amino acid
transporting mechanism.

17. Primary Active Transport
When the substance moves against the
concentration gradient by the expenditure of
energy.
It transfers only one ion or molecule & only in
one direction, hence called UNIPORT.
e.g: absorption of glucose

18. Secondary Active Transport
When the substance moves against the concentration
gradient by the energy stored by a substance
moving down the concentration gradient, the
process is called secondary transport.

19. ENDOCYTOSIS

20. Endocytosis is a process in which
a substance gains entry into cell
by formation of intracellular
vesicle by virtue of invagination
of plasma membrane and
membrane fusion takes place.
e.g. at soluble vitamins, protein
molecule, folic acid

21. ENDOCYTOSIS:
 PHAGOCYTOSIS
 PINOCYTOSIS
 RECEPTOR-MEDIATED ENDOCYTOSIS

22. PHAGOCYTOSIS:
 Cellular process of engulfing the solid
particle
 Vesicular internalization by the cell
membrane itself to form the internal
phagosome
 Vesicle = >0.75 µm in diameter
 Phagocytosis is mediated by ‘actin-
myosin contractile system’.
 Ingestion of particle ∞ size of particle
 This type of transport is utilized by
large molecular weight drugs.

23. PINOCYTOSIS
 The endocytosis in which particles or
liquid is brought into cell by forming
an invagination or vesicle called
lysosomes.
 Requires a lot of energy in form of
ATP.
 Can be in form of;
 Micropinocytosis with vesicle (<0.1µm)
 Macro pinocytosis with vacuole (0.5-5.0
µm).
 On average 2% of plasma membrane
internalized per minute.

24. RECEPTOR MEDIATED ENDOCYTOSIS:
 Also term as CLATHRIN MEDIATED
ENDOCYTOSIS.
 Process by which cells internalize molecules by
the inward budding of plasma membrane
vesicles containing protein with receptor site
specific to molecule wit receptor.
 Important in absorption across tight junction of
blood brain barrier (BBB). E.g. therapeutic

25.  Vesicle have coat made up of complex of
protein mainly:
• Cytosolic protein clathrin
• Coat protein(COP I, II)
 Clathrin coated vesicle (CCVs) form
domains of plasma membrane - clathrin
coated pits.
 concentrate large receptor responsible
for receptor mediated endocytosis.
 For example; uptake of cholesterol by
binding of LDL to LDL receptors
associated with clathrin coated pits.
First identified by MATT LION & P.
GEORGE.
Hormone receptor (insulin),
Transferrin receptor,
Antibodies, Growth factors

26. TRANSCYTOSIS:
 Process by which various macromolecules
are transported across the interior of a cell .
 Macromolecules are captured in vesicles on
one side of the cell, drawn across the cell and
ejected on the other side.
 Movement of receptor bound macromolecule
through the cell, employing both endocytosis
and exocytosis.
 Therapeutic drugs, IgA, IgG, transferrin,
 Blood capillaries are well known sites for the
transcytosis.
 Including neuron, osteoclasts, cell of
intestine.

27. To be absorbed, an oral drug encounters:
Absorption of oral drugs involves transport across epithelial
cells of the GI tract.
Low pH,
GI
secretions
Degrading
enzymes.

28.  Absorption in Mouth :
 The oral mucosa has a thin epithelium and rich vascularity, which favors
absorption.
 A drug placed between gums and cheeks (bucal administration) or under the
tongue (sublingual administration) retain longer and enhances the absorption.
 Examples:
 Nitroglycerine
 Isoprenaline
 Clonidine
 Absorption in stomach :
 Large epithelial surface but thick mucous layer limit absorption.

29.  Food especially fatty food slows down the drug absorption.
e.g: Parasympatholytic drugs are taken on an empty stomach.
 For poorly soluble drugs,
e.g: Griseofulvin food may enhance the drug absorption.
Absorption in small intestine:
 Larger surface area.
 Its membrane is more permeable than stomach.
 pH ranges 4 to 5 in duodenum and approaches 8 in ileum.
 For these reasons, most drugs are absorbed faster in the small
intestine than in the stomach.
 But the decreased blood flow and microflora may reduce absorption
in small intestine by passive diffusion.

30.  parenteral absorption is
the taking up of substances within the body by structures other than
the digestive tract.
outside the alimentary, commonly means ”the injection routes only.”
Need of Parenteral absorption:
 To get rapid and systemic effect of the drug
 To provide the needed effect when the patient (unconscious/ trauma
patient)is unable to swallow drug due to surgical alterations.
 To give nourishment when it cannot taken by mouth.

32.  Drugs given IV enter the systemic circulation directly. However, drugs
injected IM or SC must cross one or more biologic membranes to
reach the systemic circulation. If protein drugs with a molecular
mass > 20,000 g/mol are injected IM or SC, movement across
capillary membranes is so slow that most absorption occurs via the
lymphatic system.
 Perfusion (blood flow/gram of tissue) greatly affects capillary
absorption of small molecules injected IM or SC.Thus, injection site
can affect absorption rate. Absorption after IM or SC injection may be
delayed for salts of poorly soluble bases and acids.

33. Pore transport
o It is also known as connective transport or
filtration.
o Mechanism _ through the protein channels
present in the cell membrane.
o The driving force for the passage of drug through
pore transport is hydrostatic or osmotic pressure
differences across the membrane.

34. o Thus bulk flow of water along with small solid
molecules through aqueous channels. Water flux
that promote such a transport is called as solvent
drag.
o The process is important in the absorption of low
molecular weight (< 100D) , low molecular size (smaller
than the diameter of the pore) and generally water
soluble drugs through narrow , aqueous filled channels
or pores.

36. Ion pair transport
o It is another mechanism to explain the absorption
of such drugs which ionize at all pH conditions e.g.
quaternary ammonium, sulphonic acid.
o Although they have low partition coefficient values
they will penetrate the membrane by forming
reversible neutral complexes with endogenous ions
e.g. mucin of GIT

37. o Such neutral complexes have both the
required lipophilicity as well as aqueous
solubility for passive diffusion.
e.g. propranolol, a basic drug that forms an ion
pair with oleic acid and absorbed by this
mechanism.

38. FACTORS AFFECTING
ABSORPTION OF
DRUGS

39. 1. Molecular size:
•Smaller the molecular size of the drug rapid is the absorption.
• Those with a large molecular size undergo endocytosis or facilitated
diffusion, while those with smaller molecular sizes undergo diffusion or
lipid channels.
2.Degree of Ionization:
•Different drugs are either acidic or basic and are present in ionized or
unionized form, which is given by their pKa values. And it depend upon
the pH of the body .
•Acidic drugs are unionized in the acidic medium and basic drugs are
unionized in the basic medium.
•Acidic drugs are better absorbed from the acidic compartment.

40. 3. Physical Forms:
•Drugs exist as solids, liquids or gases.
•Gases (anesthesia) are rapidly absorbed than the liquids, while
the liquids (syrup or suspension form) are rapidly absorbed than
the solids (tablets or capsules).
4. Chemical Nature:
•Chemical nature is responsible for the selection of the route of
administration of drug.
•Drugs in inorganic or salt form are better absorbed than organic
forms.
5. Concentration:
•According to Fick’s law, higher the concentration more fluctuation
occurs across the membrane. The rate is less affected than the
extent of absorption.

41. 6. Dosage Forms:
Dosage forms also affect the rate and extent of absorption. It
include to process disintegration and dissolution .When these
two processes occur rapidly, the rate of absorption increases.
a. Disintegration:
•Breaking up the dosage form into smaller particles.
b. Dissolution:
•After disintegration, the drug dissolves in the gastric juices, is
called dissolution.
7. pH:
•Acidic pH favors acidic drug absorption while basic pH is
better for basic drugs.

42. 8. Presence of other Substances:
Foods or other chemical may increase or decrease the rate of
absorption. Especially for the drugs given orally. E.g.
•Vitamin C enhances the absorption of iron.
•Milk decreases the absorption of tetracycline.
•Calcium salts when given with iron salts or tetracycline interfere
with their absorption
9. GI Mobility:
•GI mobility must be optimal for absorption of oral drugs. It
should be neither increased nor decreased which may affect
the rate or extent of absorption.
10. Particle size
• Larger is the particle size, slower will be the absorption.