Biopharmaceuti
cs &
Pharmacokineti
cs
2st presentation
Lecturer: Dr. Muslim Suardi,
[Link], Apt
1.
2.
3.
4.
5.
Kelompok 2
Nova Lestari
(1411011043)
Rama saputri
(1411011046)
Anna fadhila
(1411011049)
Nur Azlin
(1411011061)
Suci Dita Ramadhani
(1401101164)
Dissolution:
is the process by which a solid solute enters in
to a solution. It is the process of dissolving
solid part (solute) in the solvent (liquid).
The time it takes for the drug to dissolve in
the fluids at the absorption site called
dissolution rate.
(Ansels Pharmaceutical Dosage Forms and Drug Delivery
Systems, 2011)
Things that affect dissolution are:
1. Temperature:
In most cases ofdissolutionof solid (solute)
in a liquid involves the absorption of heat. If the
temperature is increased then
thedissolutionwill be more & if the temperature
is decreased than thedissolution will be less.
Why do we study
dissolution?
Disintegration
Dissolution
Absorption
Drug in
the
blood
and the
body
Things that affect dissolution are:
1. Temperature:
In most cases ofdissolutionof solid (solute)
in a liquid involves the absorption of heat. If the
temperature is increased then
thedissolutionwill be more & if the temperature
is decreased than thedissolution will be less.
2. Agitation (concentration of the solvent)
Dissolutionalso depends on the
concentration of the solvent. If the solvent is
more concentrated dissolution will be less. If the
solvent is less concentrated dissolution will be
more.
3. ParticleSize
Thedissolutionrate of depends on
itsparticlesize.
Smallparticlesize,dissolutionwill be more and
large particle size, dissolutionwill be less.
The dissolution rate of drugs may be
increased by decreasing the drugs particle size.
4. Solvent selection
Dissolutionalso depends on the concentration of the solvent. In
waterdissolutionrate will be more than oily solvent.
When the dissolution rate is the rate-limiting step,
anything that affects it will also affect absorption.
Consequently, dissolution rate can affect the
onset, intensity, and duration of response and
control the overall bioavailability of the drug from
the dosage form.
(Ansels Pharmaceutical Dosage Forms and Drug Delivery Systems,
2011)
The dissolution rates of chemical compounds are
determined by two methods: the constant surface
method and particulate dissolution.
The constant-surface method
The dissolution rate obtained by this method, the
intrinsic dissolution rate, is characteristic of each
solid compound and a given solvent in the fixed
experimental conditions. The value is expressed as
milligrams dissolved per minute per centimeters
squared.
= useful in predicting probable absorptionproblems
due to dissolution rate
Particulate dissolution
A weighed amount of powdered sample is
added to the dissolution medium in a constant
agitation system. This method is frequently
used to study the influence of particle size,
surface area, and excipients upon the active
agent.
(Ansels Pharmaceutical Dosage Forms and Drug Delivery
Systems, 2011)
Drugs in solid dosage forms undergo
various stages of release from the
dosage form before it is absorbed.
These stages include disintegration,
deagregasi and dissolution.
The rate of drug reaching the
circulation system in the process of
disintegration, dissolution and
absorption, is determined by the
slowest stage of the circuit above
the so-called rate limiting step
(Shargel and Yu, 1999).
So that the solid particles
dissolved solute molecules must
first be split off from a solid
surface, then move away from the
surface into the solvent.
Depending on both the process
and how the process takes place,
the transport dissolution behavior
can be described by physics. In
terms of speed of dissolution are
involved in pure substances, there
are three basic models of general
physics (Abdou, 1989).
In discussion to understand the
mechanism of dissolution, is
sometimes used one of the
models or a combination of these
models.......
a. Model diffusion layer (diffusion layer model)
This model was first proposed by Nerst
and Brunner. On solid surfaces there is
a thin layer of liquid with a thickness ,
a negative velocity component in the
opposite direction with a solid surface
(Banakar, 1992)
Reactions at the solid-liquid surface is
rapid. Once the model solutes pass
through the interface "liquid movie the film bulk", quickly mixing will occur
and the concentration gradient will be
lost. Therefore the dissolution rate is
determined by the diffusion of
Brownian motion of molecules in the
film liguid (Banakar, 1992).
b. Model barrier interface (interfacial barrier model)
This model describes the reactions
that occur on solid surfaces and in this
case the diffusion occurs along a thin
layer of liquid (Banakar, 1992).
As a result, it is not considered the
equilibrium solid-solution, and this
should be used as a handle in
discussing this model. Processes at
solid-liquid interface is now a speed
limiter in terms of transport processes.
Transport relatively rapid diffusion
occurring static passes a thin layer
(stagnant) (Banakar, 1992)
c. Model Dankwert (Dankwert model)
This model assumes that the solute
transport occurs away from a solid
surface by means of a solvent
macroscopic packet reaches the solidliquid interface due to a swirl of
random diffusion (Banakar, 1992).
This model assumes that the solute
transport occurs away from a solid
surface by means of a solvent
macroscopic packet reaches the solidliquid interface due to a swirl of
random diffusion
The dissolution is defined as a process of
dissolution of a chemical or drug compounds
from solid dosage into a particular medium
(Wagner, 1971).
Dissolution rate of a drug is the rate of
change of the solid form be dissolved in the
media any given time. So describe the
dissolution rate of drug dissolved in the
dissolution medium (Banakar, 1992).
Conditions that May Affect Drug Dissolution
and Release: Drug and formulation related
Drug substance
Particle size
Polymorph
Surface area
Chemical stability in dissolution media
Formulation of drug product
Excipients (lubricants, suspending agents,
etc)
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Conditions that May Affect Drug Dissolution
and Release: methodology related
Medium
Volume
pH
Molarity
Co-solvents, added enzymes/surfactants
Temperature of medium
Apparatus
Hydrodynamics
Agitation rate
Shape of dissolution vessel
Placement of tablet in vessel
Sinkers (for floating products and products that stick
to side of vessel)
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Dissolution Apparatus
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Rotating basket (Apparatus
1)
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Rotating basket (Apparatus
1)
In case of none-disintegrating dosage
forms this apparatus is superior to
apparatus 2 since it constraints the
dosage form in a steady state fluid
flow
It is inferior for testing dosage forms
which contains gums due to clogging
of screen matrix
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Rotating Paddle (Apparatus
2)
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Rotating Paddle (Apparatus
2)
This apparatus is identical to
apparatus 1 except that the paddle is
substituted for the rotating basket
Frequently used for both
disintegrating and non-disintegrating
dosage forms
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Reciprocating cylinder (Apparatus 3)
One advantage of the reciprocating
cylinder is that the gastrointestinal
tract conditions can be easily
simulated, as it is easy to make time
dependent pH changes
This apparatus is most suitable for
nondisintegrating (extended release)
or delayed release (enteric coated)
dosage forms
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