PHARMACEUTICAL FACTORS AFFECTING DRUG
ABSORPTION
CONTENTS

Introduction

Disintegration Time

Dissolution time

Manufacturing/Processing variable
Method of granulation
Compression forces

Pharmaceutical ingredients and excipients

Nature and type of dosage Form

Product age and storage conditions

Summary

Introduction
Absorption of drug via aforementioned mechanism depends on the several factors grouped as
patient related factors (physiological factors and clinical factors) and Pharmaceutical
factors.Pharmaceutical factors are further classified into two categories- Pharmaceutical factors
related to physicochemical properties of drug and factors related to the formulation.
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Pharmaceutical factors affecting drug absorption
DISINTEGRATION TIME
Rapid disintegration is important to have a rapid absorption so lower disintegration time is
required.
Disintegration time of tablet is directly proportional to –amount of binder and
compression force.
It is important to note that in vitro disintegration test gives no means of a guarantee of
drugs B.A. because if the disintegrated drug particles do not dissolve then absorption is not
possible.
DISSOLUTION TIME:
Dissolution is a process in which a solid substance solubilizes in a given solvent ie… mass
transfer from the solid surface to the liquid phase.
Dissolution time is also an important factor which affect the drug absorption .
MANUFACTURING/PROCESSVARIABLES:
 Several manufacturing processes influence drug dissolution from solid dosage forms.
 For example: For tablet it is
 Method of granulation
 Compression force
Process variables
 Method of granulation and compression force are most important process variables that affect
the drug absorption of solid dosage forms. Tablets prepared by wet granulation dissolve at
faster rate than those prepared by other granulating methods. However, this method of
granulation has limitations like chemical degradation, formation of Crystal Bridge and
deleterious effect of the drying step on thermoliable drugs.
 The agglomerative phase of communition (APOC) is new development in granulation
technology that involves extensive grinding of drug so that spontaneous agglomerated
particles are formed. The granules prepared by this method have higher surface area and hence higher
dissolution rate.
 The most important factors that affect drug absorption from tablet include use of lubricants
and compression force for tableting. Lubricants are hydrophobic substances that produce
acceptable tablet. They form hydrophobic film over the drug particles and retard wetting of
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particles with gastric fluid thereby diminish drug dissolution.
 Further, hardness of tablet affects wettability that leads to long DT. The hardness of tablet
depends on method of manufacturing and binder used.
 Tablet hardness is directly affected by compression force. Tablet compressed at high
compression force are harder than tablet compressed at low or medium compression force.
High compression force increases the strength of internal structure of granules and retards
disintegration of granules.
 Compression force has inverse effect on wettability and disintegration. Higher compression
gives rise to harder tablets. However, compression force causes crushing of particle that may
result
in
higher
effective
surface
area
thereby
causing
a
decrease
in
DT.
Compression force affects hardness, porosity and density of granules that may affect drug
disintegration. Therefore, effect of compression force should thoroughly be studied at the
stage of product development.

A change in crystal form of drug during manufacturing of tablet may cause cracking of
tablet. Sometimes drug interact with solvent used in granulation and convert into solvate
forms. They are called as hydrate when water is used as solvent. The hydrate form has quite
different solubility than anhydrous form of drug. For example ampicillin trihydrate is less
absorbed than anhydrous ampicillin due to faster dissolution of trihydrate form
Fig Influence of compression force on the dissolution rate of tablets
 The compression force employed in tableting process influence density, porosity, hardness,
disintegration time and dissolution rate of tablets.
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PHARMACEUTICAL INGREDIENTS/EXCIPIENTS
 More the number of Excipients in the dosage form, more complex it is & greater the potential
for absorption and Bioavailability problems.
A) Vehicle
 Rate of absorption – depends on its miscibility with biological fluid.
 Miscible vehicles (aqueous or water miscible vehicle) causes rapid absorption e.g. propylene
glycol.
 Immiscible vehicles – Absorption depends on its partitioning from oil phase to aqueous body
fluid.
B) Diluents
 Hydrophilic diluents – Imparts Absorption
 Hydrophobic diluents – Retards Absorption
 Also, there is a drug-diluent interaction, forming insoluble complex and retards the absorption.
E.g. Tetracycline-DCP
C) Binders & granulating agent  Hydrophilic binders – Imparts hydrophilic properties to the granule surface – gives better
dissolution properties of the poorly wettable drugs. E.g. Starch, Gelatin. PVP.
 But more amount of binder increases the hardness of the tablet and retards the absorption rate.
D) Disintegrants
 Mostly hydrophilic in nature.
 Decrease in amount of disintegrants – significantly lowers B.A.
E) Suspending agents/viscosity agent
 Stabilized the solid drug particles and thus affect drug absorption.
 Macromolecular gum forms un-absorbable complex with drug e.g. Na CMC.
 Viscosity imparters – act as a mechanical barrier to diffusion of drug from its dosage form and
retard GI transit of drug.
G) Surfactants
 May enhance or retards drug absorption by interacting with drug or membrane or both.
 Physiologic surfactants – bile salts – promotes absorption – e.g. Griseofulvin, steroids
 It may decrease absorption when it forms the un-absorbable complex with drug above CMC.
H) Coating
 In general, deleterious effects of various coatings on the drug dissolution from a tablet dosage
form are in the following order.
 Enteric coat > sugar coat > non-enteric coat.
 The dissolution profile of certain coating materials change on aging; e.g. shellac coated tablets,
on prolonged storage, dissolve more slowly in the intestine. This can be however, be
prevented by incorporating little PVP in the coating formulation.
F) Lubricants
 Commonly hydrophobic in nature – therefore inhibits penetration of water into tablet and thus
dissolution and disintegration.
I) Buffers
 Buffers are sometimes useful in creating the right atmosphere for drug dissolution as was
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observed for buffered aspirin tablets.
However, certain buffer systems containing potassium cations inhibit the drug absorption as
seen with Vitamin B2 and sulfanilamide.
J) Colourants
 Even a low concentration of water soluble dye can have an inhibitory effect on dissolution
rate of several crystalline drugs.
 The dye molecules get absorbed onto the crystal faces and inhibit the drug dissolution. For
example: Brilliant blue retards dissolution of sulfathiazole

5) NATURE AND TYPE OF DOSAGE FORM
 Apart from the proper selection of the drug, clinical success often depends to a great extent on
the proper selection of the dosage form of that drug.
 For a given drug, a 2 to 5 fold or perhaps more difference could be observed in the oral bioavailability of a drug depending upon the nature and type of dosage form.
 As a general rule, the bio-availability of a drug form various dosage forms decrease in the
following order: Solutions > Emulsions > Suspensions > Capsules > Tablets > Coated Tablets
> Enteric Coated Tablets > Sustained Release Products.
Bio-availability risk and absorption of various dosage forms.
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Fig :
1.0 Introduction
Absorption of drug via aforementioned mechanism depends on the several factors grouped as
patient related factors (physiological factors and clinical factors) and Pharmaceutical factors.
Pharmaceutical factors are further classified into two categories- Pharmaceutical factors related
to physicochemical properties of drug and factors related to the formulation.
Pharmaceutical
sciences
Biopharmaceutics & Pharmacokinetics
Pharmaceutical factors affecting drug absorption
Product age and storage conditions
Product age and storage condition can also affect drug absorption. Some drug products
deteriorate or become physically unstable if stored in improper condition or kept too long and
hence drug product become ineffective. For example precipitation of drug in solution and particle
growth in suspension stored under improper storage condition adversely affect drug absorption.
Moreover, hardening of tablet stored at higher temperature may result in low absorption. The drug
product must be stored under prescribed storage conditions like cool and dry place or in the
refrigerator or in dark place. Therefore product aging and effect of storage condition of drug
absorption and stability should be studied.
3.0 Summary
Drug absorption is amount of unchanged drug that reach to general systemic circulation from the
site of administration. Drug can be absorbed by passive diffusion, pore transport, facilitated
diffusion, active transport and pinocytosis. Absorption of drug depends on various factors among
of which is pharmaceutical factors disintegration time manufacturing method, type of dosage
form, pharmaceutical ingredients and product age & storage conditions. Therefore effect these
factors on drug absorption should be studied at product development stage to design stable, safe
and effective dosage form.
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Pharmaceutical factors affecting drug absorption