ABDUL WALI KHAN UNIVERSITY MARDAN

DEPARTMENT OF PHARMACY
Biopharmaceutics assignment

Topic name
Physiochemical properties of drugs

Submitted By:
Irfan ullah
Submitted To:
Dr.Yasir shah sb
 PHYSICOCHEMICAL PROPERTIES OF THE DRUG
AFFECTING ABSORPTION
Drug Solubility and Dissolution rate
Absorption of a drug is possible only when it is present in
the solution form. This means that drugs administered orally in
solid dosage forms (tablet, capsule, etc.) or as a suspension
(already disintegrated but not dissolved) must dissolve in the
gastrointestinal (GI) fluids before absorption can occur

The natural pH environment of the gastrointestinal tract

varies from acidic in the stomach to slightly alkaline in the small
intestine. A basic drug is more soluble in an acidic medium,
forming a soluble salt. Conversely, an acid drug is more soluble
in the intestine, forming a soluble salt at the more alkaline pH.
The solubility–pH profile gives a rough estimation of the
completeness of dissolution for a dose of a drug in the stomach
or in the small intestine. Greater the lipid water solubility
coefficient (partition coefficient), more is the lipid solubility of
the drug and greater is the absorption. Less the coefficient, less
is the lipid solubility and less is the absorption. However, Water
film exists on the membranes so part of the drugs must be water
soluble to cross this water film. Drugs with benzene ring,
hydrocarbon chain, steroid nucleus and halogen groups in their
structures are lipid soluble.The rate determining steps in
absorption of orally administered drugs are:
1. Rate of dissolution
2. Rate of drug permeation through the bio-membrane.
Dissolution is the rate determining step for hydrophobic &
poorly aqueous soluble drugs.
e.g., Griesiofulvin & Spironolactone.
Permeation is the rate determining step for hydrophilic &
high aqueous soluble drugs.
e.g., Cromolyn sodium or Neomycin.

The solubility of a drug can be controlled by a proper

selection of soluble salts (rather than use of the less-soluble free
acid or base form), the selection of different crystal forms or
hydrated forms, or perhaps modifications in chemical structure.

Drug Stability
For absorption it is necessary that the drug must be stable at
the site of absorption. Two major stability problems resulting in
poor bioavailability of an orally administered drug are:
  degradation of the drug into inactive form e.g., Penicillin G
(enzymatic degradation), erythromycin (decomposition in
acidic medium).
 interaction with one or more different component(s) either
of the dosage form (excipients) or those present in the GIT
to form a complex that is poorly soluble or is unabsorbable.

Surface area and particle size

A drug dissolves more rapidly when its surface area is

increased (reduction in Partical size). Because dissolution takes
place at the surface of the solute (drug), the greater the surface
area, the more rapid is the rate of drug dissolution. This is the
reason why many poorly soluble and slowly dissolving drugs are
marketed in micronized or microcrystalline form (i.e. particle
size of 2–10mm). e.g., decreasing the particle size of digoxin
from 102µm to approximately 10µm resulted in 100% increase
in bioavailability.
For poorly soluble drugs, a disintegrant may be added to
the formulation to ensure rapid disintegration of the tablet and
release of the particles. The addition of surface-active agents
into the formulation of tablets, capsules, suspensions etc., may
increase wetting as well as solubility of the drugs. The more
commonly used wetting agents include tweens, spans, sodium
and lauryl sulfate. These agents lower the contact angle between
an aqueous liquid and a hydrophobic particle. For example,
Ceclor (cefaclor) suspension contains sodium and lauryl sulfate
as wetting agent.

Amorphism and Polymorphism

Amorphism: Some drugs can exist in amorphous form (i.e.

having no internal crystal structure). Such drug represents the
highest energy state. They have greater aqueous solubility than
the crystalline forms because a energy required to transfer a
molecule from the crystal lattice is greater than that required for
non-crystalline (amorphous form). E.g., the amorphous form of
Novobiocin is 10 times more soluble than the crystalline form.

Polymorphism: refers to the arrangement of a drug

substance in various crystal forms or polymorphs. Polymorphs
have the same chemical structure but different physical
properties, such as solubility, density, hardness, hygroscopicity
and compression characteristics. Some polymorphic crystals
have much lower aqueous solubility than the amorphous forms,
causing a product to be incompletely absorbed.
Chloramphenicol, for example, has six crystal forms, and when
given orally as a suspension, the drug concentration in the body
was found to be dependent on the percent of β-polymorph in the
suspension. The β form is more soluble and better absorbed. In
general, the crystal form that has the lowest free energy is the
most stable polymorph. Some polymorphs are metastable and
may convert to a more stable form over time. A change in
crystal form may cause problems in manufacturing the product.
For example, a change in the crystal structure of the drug may
cause cracking in a tablet or even prevent a granulation from
being compressed into a tablet.

State of hydration

The state of hydration of a drug molecule can affect some

of the physicochemical properties of a drug. One such property
that is significantly influenced by the state of hydration is the
aqueous solubility of the drug. Often the anhydrous form of an
organic compound is more soluble than the hydrate (with some
exceptions). This difference in solubility is reflected in
differences in the dissolution rate. E.g., erythromycin hydrates
have quite different solubility compared to the anhydrous form
of the drug. Ampicillin trihydrate, on the other hand, was
reported to be less absorbed than the anhydrous form of
ampicillin because of faster dissolution of the latter.

Miscellaneous

 Dosage forms affect the rate and extent of absorption. A

drug can be given in the form of suspensions, tablets,
capsules etc. The rate of absorption is different from
different dosage form. Based on the dosage form, the
variation could be depicted as:
Solution > Suspensions > Capsules > Compressed Tablets
> Coated Tablets
 According to Fick’s law, higher the concentration more
flux occurs across the membrane. The rate is less affected
than the extent of absorption.

 Drugs in inorganic form are better absorbed than organic

forms e.g. iron in Fe+2 is better absorbed than Fe+3

Refrences…….

 LEON SHARGEL
 KULKARNE
 D M BHARMAKAR