Physicochemical drug properties on the rate and

extent of systemic absorption

Group I
Riche Azizah 1111011007
Ramzil Huda 1111012042
Arizkha Fitri 1111013006
Istianah Al-Fikriyah D 1111013010
Fitria Rizky 1111013019
Introduction
Absorption of the active substance is the influx of drug
molecules into the body or into the blood circulation
to the body after passing the biological barrier
(Aiache, et al., 1993).
In order for a drug to reach the workplace in tissue or
organ, the drugs must pass through various cell
membranes. In general, having a cell membrane
lipoprotein structure that acts as a semipermeable
membrane lipids (Shargel and Yu, 1985).
 Drugs are freed from dosage form may
not be absorbed, if the drug bound to
the skin or mucosa called adsorption. If
the drug to penetrate into the skin, but
not into the capillary so called
penetration. If the drug permeated /
penetrate the capillary walls and into
the blood stream is called absorption.
(Joenoes, 2002)
Physicochemical properties of
drugs that affect absorption
Size and shape of the particles
Very small molecules and small ions pass through the
membrane to move quickly, as it has a pore membranes
and vice versa, a very large macromolecules not pass
through the cell membrane or passing through but the
number is very small.
Drugs that bind strongly to the protein are as
macromolecules and does not pass through the cell
membrane. This phenomenon often occurs when the drug
is bound to plasma proteins.
(Shargel and Yu, 1985)
 Both equations Noyes and Whitney or
Nernst and Bruner stated rate of dissolution
is directly proportional to the effective
surface area of the active substance in
contact.
A decrease in the particle size of active
substances will increase the contact surface
area of the active substance and solvent.
(Shargel and Yu, 1985)
 A decrease in particle size can increase the rate
of absorption when downsizing affects the
dissolution process. Reduction of particle size
plays a role not only on the rate of absorption but
also on his degree of solubility of a compound.
The size of the particles proved to significantly
affect oral absorption profile of certain drugs such
as griseofulvin, nitrofurantoin, spironolactone,
and procaine penicillin.
(Farmasi.unud.ac.id)
 The geometry also affects the particle
surface area and during the dissolution,
the surface changes constantly. the
calculation is usually considered that
the solute particles retain geometric
shapes.
(Shargel and Yu, 1985)
 Solubility
A physical-chemical properties that are
important from a drug substance is
solubility, especially solubility in water
systems. A drug must have a solubility in
water that is therapeutically efficacious. In
order for a drug into the circulation system
and produce a therapeutic effect, it must
first be in solution.
(Shargel and Yu, 1985)
 The compounds are not soluble often
show incomplete absorption or erratic. If
the solubility of the drug is less than
desirable, consideration should be given to
improve the solubility.
The degree of solubility in water also
affect the rate of dissolution. in general, the
drugs in the ionized salt form which can be
more soluble in water than the acid or free
base.
(Shargel and Yu, 1985)
 Compound dissolves in water and fat in
different ways:
- Water form hydrogen bonds with ionic or
nonionic polar compounds through the -
OH, -NH, -SH or C = O, or with a pair of free
electrons in the atom N or O.
- Between fat (or nonpolar solvent) with a
nonpolar compounds occur hydrophobic
interactions and van der Waals bonding.
(rinaherawati.wordpress.com)
There are several ways to affect solubility:
Salt Formation
Aims to change the salt formation of acid and alkaline
compounds poorly soluble in water into salt form in
order to obtain an increase in the rate of dissolution.
Ester formation
Intended to avoid decomposition of the active
substance in the stomach "erythromycin or
lincomycin", impede or prolong the action of various
active substances and cover the bad taste "of
chloramphenicol palmitate ester
(Farmasi.unud.ac.id)
 Complex formation
Can increase the solubility of the complex but can
not cross the membrane, but due to the complex bond
is reversible bonding, so complex can be disconnected
and re-absorbed by the membrane.
Examples :
- Fe metal absorption in the gastrointestinal tract can
be enhanced by citric acid complex formation and
acid-ethylenediamine tetrasetat
- The formation of clathrates or "caged compounds"
that trap other compounds in its structure space gallic
acid, thiourea, amylose, and zeloit
(Farmasi.unud.ac.id)
 Crystalline, polymorph and amorphous forms
The drug can also be in the form of more than
one crystal form is called polymorph. Reviews
These polymorphs have identical chemical
structure, but shows different dissolution kinetics.
In general more rigid crystal form, hard, and is
thermodynamically more stable than amorphous
forms. so the drug in amorphous form shows a
faster dissolving form of the drug in crystalline
form.
(Shargel and Yu, 1985)
 Solvat and hydrat
During crystallization, the water
molecules and polar molecules can bind
strongly with the active ingredient to
produce solvates, hydrates are formed when
the solvent is water. Anhidrat compounds
generally show higher dissolution rate
slammed the form of hydrates. Hydrate or
solvate can be formed on the manufacture
or storage of drugs.
(Farmasi.unud.ac.id)
 Derajat ionisasi
Most drugs are weak electrolytes which
form weak acid or weak base. In a weak
electrolyte solution will be ionized. The
degree of ionization depends on the pH of
the solution and pKa drugs. For acid drugs,
low pKa means relatively strong, while for
alkaline drugs, high pKa relatively strong.
(Shargel and Yu, 1985)
 Non ionic form are generally soluble
both in fat so readily diffuses across the
membrane. While the form of ions, across
the membrane is difficult because of poorly
soluble in fat. At the level of steady drug
levels form ion - ion are the same on both
sides of the membrane, while the ionic form
of the drug concentration depends on pH
differences on both sides of the membrane.
(Shargel and Yu, 1985)
 Ionization is an important characteristic
electronic structure, as it affects drug
absorption and ability to penetrate cell
membranes.
Transport pharmacokinetics of the drug
during phase is determined by the increased
solubility of the ionic form and increase the
ability of the anionic form penetrate the
lipid bilayer membrane layer.
(Shargel and Yu, 1985)
 The degree of ionization is expressed by
the Henderson-Hasselbalch equation:

% Unionized = 100 / (1 + antilog [pH - pKa])

(Shargel and Yu, 1985)
References
Aiache, J.M. & J. Devissaguet. 1993. Farmasetika 2
: Biofarmasi. Terjemahan Soeratri W, ed 2. Airlangga
University Press : Surabaya.
Zaman, N. dan Joenoes. 2002). ARS Prescribendi
Resep yang Rasional. Surabaya: Airlangga University
Press.
I M. A. Gelgel Wirasuta. Farmasi.unud.ac.id
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