Factors affecting absorption of drugs.

1. Diwakar chudal
B.Pharmacy , Institute of Medicine (IOM)

2. Definition
 Drug absorption is defined as the process of
movement of unchanged drug from the site
of administration to systemic circulation.

3.  Excipients.
 Nature and type of dosage
form.
 Storage conditions.

4.  Non-drug components which are added
during formulation of drug are called
excipients.
 Excipients are added during drug formulation
because:
 Ensures physico-chemical stability.
 Gives uniformity to composition.
 Gives optimum bioavailability.
 Gives suitable colouration and taste.

5.  Despite their importance in the drug
formulation, excipients can highly influence
the absorption of drugs.
 More the number of excipients in a dosage
form, more complex the drug becomes and
more likely to show problems in drug
absorption and bio-availability.

6.  Most commonly used excipients during
formulation of dosage form are:
Vehicle, diluents, binders or granulating
agents, disintegrants, lubricants, coatings,
suspending agents, surfactants, buffers,
complexing agents, colorants, sweetning
agents, precipitation inhibitors, etc

7.  Vehicle or solvent system is the major
component of liquid oral and parenteral
dosage form.
 Basically, 3 types of vehicles are used
▪ Aqueous vehicles (water, syrup, etc)
▪ Non-aqueous water-miscible vehicles (propylene,
glycol, glycerol, etc)
▪ Non-aqueous water-immiscible vehicles (vegetable oils)

8.  Aqueous and water miscible vehicles are
miscible with the body fluids so the drugs
from them are rapidly absorbed.
 Absorption of drugs in different vehicles
follows the order :
water-miscible vehicles > aqueous vehicles
>water-immiscible vehicles.

9.  Absorption of a drug from a viscous vehicle is
slower in comparison to non-viscous vehicle.
 Thus, nature of vehicles and viscosity of
vehicles is also one of the factor affecting the
drug absorption.

10.  Diluents are commonly added to tablets and
capsule formulations if the required dose is
inadequate to produce necessary bulk.
Inorganic Organic

11.  Organic diluents:
Starch, lactose, microcrystalline cellulose, etc
 Inorganic diluents:
Dicalcium phosphate (DCP) is most common.
 Sometimes Drug-diluent interactions alters the
absorption of drug.
Example:
Tetracycline and DCP when interacts, divalent
calcium-tetracycline complex is formed which is
poorly soluble and thus unabsorbable.

12.  Granulating agents are the substance which
are used to hold powders together to form
granules.
 It ensures that the tablet remains intact after
compression.
 Starch, cellulose derivatives, gelatin, sugar
solutions,etc are most common granulating
agents.

13.  Large amount of such granulating agents
increases hardness and decreases dissolution
rates of tablets and hence decreases the rate
of absorption.
Example:
PEG 6000 when binds with phenobarbital, it
forms complex compound with very low
solubility.

14.  Disintegrants are the substance which increases the
dissolution of tablets in water.
 When drug comes in contact with water, disintegrants
helps to overcome the cohesive force between drug
molecules and dissolution of tablets takes place in
aqueous medium.
 However, adsorbing disintegrants like bentonite and
vegum should be avoided with low dose drugs like
digoxin, alkaloids and steroids since a large amount of
dose is adsorbed and only a small fraction is available
for absorption.

15.  Lubricants are added to tablets to reduce
interparticle friction and sticking.
 Also called as anti-frictional agents.
 Lubricants are mostly hydrophobic in nature
and thus inhibits the penetration of water
into the tablets.
 Lubricants are applied by coating it over the
surface of tablets.

16. Coating:
 The process of applying one substance on the
surface of another.
 Deleterious effects of various coatings on
drug dissolution from a tablet follows the
order:
▪ Enteric coat > suger coat > non-enteric film coat

17.  Suspending agents are the substance which
stabilize the solid drug particles by reducing
their rate of settling through an increase in the
viscosity of the medium.
 Also called as viscosity imparters.
 Mostly used suspending agents are hydrophilic
polymers like:
▪ Vegetable gums (eg. Acacia)
▪ Semi-synthetic gums(eg. CMC, MC)

18.  An increase in viscosity by some suspending
agents acts as a mechanical barrier to the
diffusion of drug from the dosage form into
the bulk of GI fluid and from GI fluid to the
mucosal lining.
Example:
 CMC forms unabsorbable complexes with
amphetamine.

19.  Surfactants are used in drug formulations as
wetting agents, solubilizers,etc
 Surfactants may either increase or retard the
drug absorption interacting with drug
molecules.
 Surfactants usually increases drug absorption
by increasing membrane permeability of the
drug.

20.  Decrease in absorption of drug in the
presence of surfactant is due to formation of
unabsorbable drug-surfactant complex at
surfactant concentrations above the critical
concentration.
 Thus, higher surfactants concentration
always decreases the rate of drug absorption.

21.  Buffers are the solutions whose PH value
remains almost constant after addition of
small amounts of acids or alkali.
 Buffers are sometimes useful in increasing
the rate of dissolution of drug. Eg.buffered
aspirin tablets.
 But, certain buffer systems containing
potassium cations inhibits drug absorption as
seen in vit B2 and sulphanilamide.

22.  Inhibitory effect of the various buffer cations
on the drug absorption follows the order:
K+ > NH4
+ > Li+ > Na+ >TRIS+

23.  In some drugs, complexing agents are added
to alter the physico-chemical and bio-
pharmaceutical properties of a drug.
 A complexed drug may have different
stability, solubility, molecular size, diffusion
rate, etc
 Examples of complexation which increases
the drug absorption are:

24. Ergotamine tartarate – caffeine complex. (increases
dissolution)
Caffiene-PABA complex. (increases membrane
permeability)
• However, complexation can sometime decrease the
drug absorption due to formation of poorly
absorbable complex
Eg. Complexation of tetracycline with divalent and trivalent
cations like calcium, iron, magnesium, aluminium,etc
decreases absorption.

25.  Colorants are added in drug formulations to
mask the unattractive original colour of a drug.
 But, colourants can also largly affect the drug
absorption.
 Very low concentrations of water soluble dye
can have an inhibitory effect on dissolution rate
of several crystalline drugs
Eg. Brilliant blue dye retards dissolution of
sulpathiazole.

26.  When concentration of free drug increases
above the saturation, it results in
supersaturation which leads to drug
precipitation or crystallization.
 PVP, HPMC, PEG, PVA, etc are some polymers
which prevents drug precipitation by:
Increasing the viscosity of vehicle
Adsorbing on the faces of crystals thus reducing
crystal growth.

27.  The rate of absorption and bio-availability of
certain drug largely depends on the proper
selection of dosage form of that drug.
This is due to the relative rate at which a particular
dosage form releases the drug to the biological
fluids and membrane.
 As a general rule, bio-availability of a drug
from various dosage forms decreases in the
following order:

28.  Solutions > emulsions > suspensions >
powders > capsules > coated tablets >
enteric-coated tablets > sustained-release
tablets.
 Thus, absorption of a drug from solution is
fastest with least potential for bioavailability
problems whereas absorption from
sustained-release product is slowest with
greatest bioavailability risk.

29.  A number of changes in the physico-chemical
properties of a drug can result due to storage
conditions which can adversely affect absorption
and thus bio-availability.
 When shelf-life of the solutions becomes long,
solubility of drug changes and precipitation can
occur.
 Similarly, decrease in rate of dissolution occurs
in suspension dosage form

30.  High temperature and humidity results in
increase in hardness of tablets which
decreases the rate of absorption.
 Therefore, storage conditions and product
age has significant role in the absorption of
drug from different dosage forms.

31. THANK YOU