1. ABSORPTION OF
DRUGS
SUBMITTED BY
JASEEM.K
1ST YEAR M-PHARM

2. TOPICS
 DEFINITION
 STRUCTURE OF GIT
 MECHANISM OF TRANSPORT
 FACTORS AFFECTING ABSORPTION
 -PHYSIO-CHEMICAL FACTORS

3. DEFINITION
 It is defined as the process of movement of
unchanged drug from the site of
administration to the systemic circulation.
 There always present a correlation between
plasma concentration of a drug & the
therapeutic response & thus, absorption can
also be defined as the process of movement
of unchanged drug from the site of
administration to the site of measurement.
i.e., plasma.

5. STRUCTURE OF CELL
MEMBRANE

6. M ECHANISM OF DRUG
ABSORPTION
1. Passive diffusion
2. Carrier- mediated transport:
a) .Active diffusion
b). Facilitated diffusion
3. Pore Transport
4. Ionic or Electrochemical diffusion
5. Ion-pair transport
6. Endocytosis

7. PASSIVE D IFFUSION
Characters
 common.
 Occurs along concentration
gradient. Non selective
 Not saturable
 Requires no energy
 No carrier is needed
 Depends on lipid solubility.
 Depends on pka of drug - pH of
medium.

8. Expressed by Fick’s first law of diffusion -
“The drug molecules diffuse from a region of
higher concentration to one of lower
concentration until equilibrium is attained & the
rate of diffusion is directly proportional to the
concentration gradient across the membrane”.
dq/dt = D A Ko/w (Cgit – Cplm)/Vh
Sink condition
dQ/dt =P CGIT

9. Active Absorption
 Relatively unusual.
 Occurs against concentration
gradient.
 Requires carrier and energy.
 Specific
 Saturable.
 Iron ,K , Na , Ca
 Uptake of levodopa by brain.

10. PASSIVE AND ACTIVE TRANSPORT

11. FACILITATAED DIFFUSION
 Occurs along the concentration gradient
 Require carriers
 Saturable
 Stucture specific
 No energy required
 Mixed order kinetics
 monosaccharides , amino acids , vitamins

13. P ORE T RANSPORT
 Also known as convective transport, bulk flow
or filtration.
 Important in the absorption of low mol. Wt.
(less than 100). Low molecular size (smaller
than the diameter of the pore) & generally
water-soluble drugs e.g. urea, water & sugars
 The driving force for the passage of the drugs
is the hydrostatic or the osmotic pressure
difference across the membrane.

14. Rate of absorption via pore Transport depends on
the number & size of the pores, & given as follows:
dc = N. R2. A . ∆C
dt (η) (h)
where,
dc = rate of the absorption.
dt
N = number of pores
R = radius of pores
∆C = concentration gradient
η = viscosity of fluid in the pores

15. I ONIC OR E LECTROCHEMICAL
DIFFUSION
 Charge on membrane influences the
permeation of drugs.
 Molecular forms of solutes are unaffected by
the membrane charge & permeate faster
than ionic forms.
 The permeation of anions & cations is also
influenced by pH.

16.  Once inside the membrane, the cations are
attached to negatively charged intracellular
membrane, thus giving rise to an electrical
gradient.
 If the same drug is moving from a higher to
lower concentration, i.e., moving down the
electrical gradient , the phenomenon is
known as electrochemical diffusion
 Thus, at a given pH, the rate of
permeation may be as follows:
Unionized molecule > anions >
cations

17. I ON PAIR TRANSPORT
 It is another mechanism to explain the absorption
of such drugs which ionize at all pH condition.
 Quaternary ammonium compounds, sulfonic acid
 Although they have low o/w partition coefficient
values, they will penetrate the membrane by
forming reversible neutral complexes with
endogenous ions. e.g. mucin of GIT.
Such neutral complexes have both the required
lipophilicity as well as aqueous solubility for passive
diffusion.
This phenomenon is known as ion-pair transport.

18. E NDOCYTOSIS
 It involves engulfing extracellular materials
within a segment of the cell membrane to
form a saccule or a vesicle (hence also
called as corpuscular or vesicular transport)
which is then pinched off intracellularly
 Fats , starch , oil soluble vitamins
 Insulin
 Absorbed into lymphatic circulation –
bypassing first pass hepatic metabolism

19. In endocytosis, there are two process
A) Phagocytosis
B) Pinocytosis

20. P INOCYTOSIS
 This process is important in the absorption of oil
soluble vitamins & in the uptake of nutrients.

21. FACTORS AFFECTING DRUG ABSORPTION
• PHYSIOLOGICAL FACTOR
PATIENT RELATED
FACTORS
• CLINICAL FACTOR
•Physico-chemical factors
PHARMACEUTICAL
FACTORS
•Formulation factors

22. P HYSICO - CHEMICAL FACTORS
 Drug solubility and dissolution rate.
 Particle size & effective surface area.
 Polymorphism & amorphism.
 Pseudopolymorphism
 Salt form of the drug
 Lipophilicity of the drug
 pKa of the drug & Ph
 Drug stability

23. D RUG SOLUBILITY &
D ISSOLUTION RATE
 Rate determining process in the absorption of
orally administered drugs are :-
1.rate of dissolution
2.rate of drug permeation through the
biomembrane
Hydrophobic-RDS- Dissolution
Eg:- griseofulvin , spiranolactone
Hydrophilic-RDS-permeation rate limited
Eg: - cromolyn sodium or neomycin

24. P ARTICLE SIZE & EFFECTIVE
SURFACE AREA
 Particle s size and surface area of a solid drugs are
inversely related to each other
 Smaller particle size-> greater surface area->rapid
dissolution
 Micronization –grater surface area-rapid
dissolution
hydrophilic drugs-follows
 Eg:-griseofulvin, spiranolactone

25.  Hydrophobic drugs-micronization-decrease
in effective surface area-fall in dissolution
rate
 Causes
 Adsorption of air to surafce
 Particle reaggregation
 Surface charge
 Eg:- aspirin , phenacetin
 In that case add-surfactants –tween 80
 hydrophilic diluents-PEG ,PVP
 DEXTROSE

26. D) POLYMORPHISM AND AMORPHISM
POLYMORPHISM
When substance exists in
different crystalline
forms, it is polymorphism.
Plot of Cp Vs Time for three formulations of
Chloramphenicol Palmitate

27. AMORPHISM
 These drugs can exist with no internal
crystal structure.
 Such drug represents the highest energy
state and can be considered as super
cooled liquids and thus have greater
solubility. E.g. Novobiocin.
 Thus, the order of Dissolution & hence
Absorption for different solid dosage
forms is amorphous > meta-stable >
stable.

28. F) SALT FORM OF THE DRUG
Salt of weak acid and weak
bases have much higher
aqueous solubility than the
free acid or base.
Therefore, if the drug can be
given as a salt, the
solubility can be increased
and the dissolution thus
can be improved. Fig 1. It shows the dissolution
Profile of various salts

29. D RUG P K A , LIPOPHILICITY & G I
PH
 According to pH PARTITION THEORY, the process of
absorption of drug compounds of molecular weight
greater than 100 Daltons transported across the
biomembrane by passive diffusion depend upon the
following factor
 Dissociation constant of the drug i.e., pKa of the drug
 Lipid solubility of the unionized drug i.e., Ko/w
 pH at the absorption site
 The amount of drug that exist in unionized form is a
function of dissociation constant(pKa) of the drug and pH
of the fluid at the absorption site.

30. FOR WEAK ACIDS
FOR WEAK BASE

31. PREDICTION BASED ON THEORY
 FOR WEAK ACIDS
 1.very weak acids(pKa>8)– unionized at all ph—absorption is rapid—
indipendantof GI ph
 Eg:-phenytoin , ethosuximide
 2.acids in the pKa range 2.5 to 7.5 largely affected by ph change—
absorption ph dependant—better absorbed from acidic conditions
of stomach (ph<pKa)where they largely exist in unionized form
 Eg:-aspirin , ibuprofen
 3.strong acids (pKa<2.5) ionized at entire ph range of GIT ---remain
poorly absorbed
 Eg:-cromolyn sodium

32. For basic drugs
1.Very weak bases(pKa<5) unionized at all pH values ---
absorption is rapid and pH indipendant
Eg:-diazepam , nitrazepam
2.Bases in pKa range 5 to 11 is pH dependant –better
absorbed from the
Relatively alkaline conditions of the intestine
Eg:-chloroquine , imipramine
3. Strong bases (pKa>11) ionized at entire pH range –
poorly absorbed
Eg:-mecamylamine guanethidine

33. 1)pH-partition Hypothesis
Simplest principle:
Unionised Higher
Drug: Absorption
Ionised Low
Drug: Absorption

34. • Weak Acid pKa>8
High Pentobarbital & aspirin
• Weak Base pKa<5
Absorption (Theophylline, caffeine,
codeine)
Low • Strong Acid(Disodium
cromoglyate)
absorption • Strong Base(Guanethidine)

35. LIPOPHILICITY
 Only unionized drug having sufficient lipid
solubility is absorbed into systemic circulation.
 So drug should have sufficient aqueous solubility
to dissolve in the fluids at the absorption site and
lipid solubility high enough to facilitate the
partitioning of the drug in lipoidal membrane
and into systemic circulation.

36. D RUG STABILITY
 Two major stability problems are
 1.degradation of the drug into inactive form
 2.interaction with one or more component
either of the dosage form or those present in the
GIT to form a complex that is poorly soluble

37. REFERENCES
 Brahmankar D.M;Jaiswal Sunil.B;
“Biopharmaceutics and Pharmacokinetics–A
Treatise, second edition 2009.
 A Mechanistic Approach to Understanding the
Factors Affecting Drug Absorption: A Review of
Fundamentals Marilyn N. Martinez, PhD, and
Gordon L. Amidon
 overview of factors affecting oral drug
absorption BY Nai –Ning Song, Shao u zhang