Name : Mutiara Farida

Class : V A
ID : 1201002
STIFARM PADANG

Dissolution (the drug release from the

dosage form) is a very important thing for
all preparations, whether made in
conventional, solid oral dosage forms in
general, as well as dosage forms with
modified release, and may be the ratelimiting step for the absorption of drugs
given orally.

Concept dissolution
Dissolution refers to the process when the
solid phase (eg tablets or powder) into the
solution phase, such as water.
In essence, when the drug dissolves,
separating solid particles and molecule by
molecule mixed with liquid and seems to be
part of the liquid Dissolution of drugs a
process when the drug molecules were
released from the solid phase and enter into
the solution phase.

release Dissolution, The physicochemical is

the process by which solid phase into the
solvent to produce a solution.
Dissolution of drug compounds is a multistep
process that involves a multi-heterogeneous
reaction / interaction between solute-solute
phase (solute-solute) and solvent-solvent
phase and the solute-solvent interface.

Which is a heterogeneous reaction process

overall mass transfer can categorized as
a) the removal of the solute from the solid
phase,
b) accommodation of the solute in the liquid
phase, and
c) diffusive and / or convective transport of
solutes from the solid / liquid interface to the
bulk phase.
Based on the perspective of the dosage form,
dissolution of the active substance is not a
disintegration of the dosage form. (Kramer et
al.
2005).

Correlation of in vitro - in vivo is a predictive

mathematical model that describes the
relationship between the in vitro properties of
an oral dosage form (usually large rate or
dissolution / drug release) and related
responses in vivo (eg, plasma drug
concentration or amount of drug absorbed )
Patterns of drug release and dissolution
generally divided into 2 groups: the zero-order
release and first order.
Obtained from the zero-order release of the
dosage form is not berdisintegrasi, such as
topical delivery systems / transdermal depot
implantation systems, or systems with
controlled drug delivery.

Dissolution rate data will only be meaningful

if the test results in a sequence of the same
stocks, consistent within acceptable limits.
Dissolution test should give reproducible
results, even if carried out in different
laboratories by different personnel.
Therefore, to achieve high reproducibility,
all the variables that can affect the test
should be well understood by the controlling
possibilities.

The factors that affect the rate of dissolution a

drug from the preparations can include:
_ The factors related to the physico chemical
properties of the drug
_ The factors related to the drug formulation
_ The factors associated with dosage forms
_ The factors related to the dissolution test
equipment
_ The factors related to the test parameters
disolus
_ Various other factors

Dissolution rate factors affecting drug related

physicochemical properties
_ Factors affecting solubility
_ Polymorphism
_ The state of amorphous and solvate
_ Free acid, free base, or a salt form
_ The formation of complexes, solid solutions,
and
mixtures eutektikum
_ The particle size
_ surfactants

Factors affecting surface area (available) for

dissolution:
_ The particle size
_ Variable-making
Some physicochemical properties of active
substances that affect the dissolution
characteristics are:
_ Ionization constants (pK),
_ Solubility as a function of pH, the stability of
the
solution as a function of pH, Particle
size, Crystal
form, Ionic strength, Ionized
form, and Buffer effect .

Factor affecting the associated dissolution rate

formulation development method :
_ The number and types of excipients, such as
neutral salt
_ Type of manufacture of tablets used
_ Granule size and granule size distribution
amount
and type of crushers and methods
_ mixing
_ The amount and type of surfactant (if added)
as
well as the mixing method
_ Style compression and compression speed.

Tool Indonesian Pharmacopoeia dissolution

test according to the fourth edition:
_ Tool basket type dissolution test (basket)
_ Tool paddle type dissolution test (paddle)
_ Tool drug release test (USP 29, NF 24):
_ Drug release testing devices such as
baskets
(basketball)
_ Drug release testing devices such as paddle
(paddle)

Test equipment such as reciprocating cylinder

drug release
_ Drug release testing devices such as flowthrough
cell
_ Drug release testing devices such as paddle
over disk
_ Test equipment in the form of drug release
cylinder
(cylinder)
_ Test equipment such as reciprocating holder
drug release

The dissolution test determines the

cumulative amount of drug that goes into
solution as a function of time. As shown in
Figure 1, dissolution of drug from a dosage
form involves at least two consecutive steps:
liberation of the solute or drug from the
formulation matrix (disintegration), followed
by dissolution of the drug (solubilization of the
drug particles) in the liquid medium. The
overall rate of dissolution depends on the
slower of these two steps.

The relative difference in rates should be carefully

considered when designing the dissolution
method. The cohesive properties of the
formulated drug play a key role in the first step of
dissolution. For solid dosage forms, these
properties include disintegration and erosion;
whereas for semisolid or liquid formulations, the
dispersion of lipids or partitioning of the drug from
the lipid phase is the key factor. If the first step of
dissolution is rate limiting, then the rate of
dissolution is considered to be disintegration
controlled. Careful assessment of the intrinsic rate
of dissolution and the effect of various aspects of
the formulation (e.g.,release profiles from
precompressed granules, impact of compression
force, porosity, and lubrication) can reveal the
relative contribution of the disintegration step to
the overall dissolution of the drug form.

In the second step of dissolution

solubilization of the drug particlesthe
physicochemical properties of the drug such
as its chemical form (e.g., salt, free acid,
free base) and physical (e.g., amorphous or
polymorph, and primary particle size) play
an important role. If this latter step is rate
limiting, then the rate of dissolution is
intrinsic dissolution controlled. This is the
case for most poorly soluble compounds in
IR formulations. For poorly soluble
compounds in solubilized formulations, in
vivo precipitation also may need to be
considered when developing a dissolution
test method, in particular for establishing
an IVIVR or IVIVC.

Dissolution is a process in which a solid

substance solublizes in a given solvent i.e.
mass transfer from the solid surface to the
liquid phase. Several theories to explain
drug dissolution have been proposed some
of the important ones are
Diffusion layer model /film theory.
Danckwerts model/penetration (or)
surface renewal theory.
Interfacial barrier model/double barrier (or)
limited solvation theory.

According to Noyes-Whitneys Equation:

dc/dt =k s(cs-c)-----------------------(1)
Where :
dc/dt= Dissolution rate of the drug
K= Dissolution rate Constant
Cs = Concentration of drug in the stagnant
layer
C = Concentration of drug in the bulk of the
solution at time t
S =Surface area of the particles

When a solid is introduced into the

dissolution medium, the volume of fluid
immediately adjacent to its solid surface gets
saturated with the drug. The thin stationary
film of solution around the solid surface is
called diffusion layer the concentration in this
layer is equal to cs. The thickness of the
diffusion layer is h .The dissolution rate
constant rate can be expressed as
K= D/h -----------------------(2)
Where :
D = Diffusion coefficient of the drug in solution
H = Thickness of the diffusion layer

Danckwerts apposed the existence of stagnant

layer by assuming that turbulence in the
dissolution medium exists at the solid/liquid
interface.
He suggested that the agitated fluid contains
macroscopic mass of eddies (or) packets reach
the solid/liquid interface in a random fashion
due to eddy currents, absorb the solute by
diffusion and carry it to the bulk of the solution.
Such solute containing packets are continuously
replaced with new packets of fresh solvent due
to which the drug concentration at the
solid/liquid interface never reaches cs and has a
lower limiting of ci.since the solvent packets are
exposed to new solid surface each time, this
theory is also called surfacerenewal theory

Danckwerts model is expressed by equn :

V dc/dt = dm/dt = A (Cs-Cb). (D)
Where :
V=volume of dissolution medium.
dc/dt=dissolution rate of the drug.
m=mass of solid dissolved.
A=surface area of the dissolving solid.
Cs = Concentration of drug in the stagnant
layer.
Cb = Concentration of drug in the bulk of the
solution at time t.
D=diffusion coefficient (diffusivity) of the drug.
= rate of surface renewal(or)the interfacial
tension.

The diffusions layer model and Danckwerts model

are based on two assumptions.
1.Rate determining step that contains dissolution in
the mass transport.
2.solid-soln equilibrium is achieved at the soild liquid
interface.
According to the interfacial barrier model:
An intermediate concentration can exist at the
interface as result of solvation mechanism and
function of solubility rather than diffusion. When
considering the dissolution of a crystal, each face of
the crystal will have a different interfacial barrier such
a conceptis given by the following equn.
G=Ki(cs-cb)

Where :
G=dissolutionte rate per unit area
Ki =effective interfacial transport constant.
Cs = Concentration of drug in the stagnant
layer
Cb =Concentration of drug in the bulk of the
solution at time t
In this theory, the diffusity D may not be
independent of saturation concentration cs.
Therefore the interfacial model can be
extended to both diffusion layer model and
Danckwerts model.

A Text Book Biopharmaceutics and

pharmacokinectics by Gibaldi
A Text Book of Principles and applications
of Biopharmaceutics and
pharmacokinectics by Dr.H.P.Tipins &
Dr.Amirta Raj.
A Text Book of Physical Pharmaceutics by
C.V.S Subrahmanyam
Indonesian of pharmacope
USP 29, NF 24

Thank you