3. DISSOLUTION MECHANISM
• 1. Interfacial reaction that results in liberation of solute molecule from the solid phase,
The solution in contact with solid will become saturated (Cs).
• 2. The solute molecules migrate through the boundary layers surrounding the crystal
to the bulk of solution, at which concentration is (C).
• Boundary layer is nearly static and surround all wetted surface of the solid.
• Mass transfer is slowly through the boundary layer to the bulk of solution.
4. DISSOLUTION MECHANISM
• Interfacial reaction that results in liberation of
solute molecule from the solid phase, The solution
in contact with solid will become saturated (Cs).
• The solute molecules migrate through the
boundary layers surrounding the crystal to the bulk
of solution, at which concentration is (C).
• Boundary layer is nearly static and surround all
wetted surface of the solid.
• •Mass transfer is slowly through the boundary layer
to the bulk of solution.
5. NOYES-WHITNEY EQUATION
The rate of dissolution will depend on the slowest step,
migration through
boundary layer Where K is the dissolution rate constant
• k = DA/δ
• Cs is the concentration of the solute at surface available
for migration
• D is the diffusion coefficient (m2/s)
• A is the area available for molecular migration
• δ is the thickness of the boundary layer
6.
7. Mechanism of dissolution
Dissolution determines the cumulative amount of drug
that goes into solution as a function of time
Steps involved
liberation of the solute or drug from the formulation
matrix (disintegration)
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
8. RELATIONS
SMALLER THE DRUG PARTICLE, GREATER THE
SURFACE AREA.
1.PARTICLE SIZE INVERSELY PROPOTIONAL TO :
SURFACE AREA
ABSORPTION
BIOAVALABILITY
2.PARTICLE SIZE IS DIRECTLY PROPORTIONAL TO:
DOSE ADMINISTERED
FLOW PROPERTY.
9. Reduction in Particle size improve solubility of
drug.
Basically reduction in particle size increase contact
surface area of the particle, there by ultimately it
increase rate of solubility of drug.
Reduction Of Particle size
04/05/2012 9
10. Conclusion:
• Conclusion As the particle size and powder
properties ultimately effects the drug release from
the dosage form, importance should given to it
while designing the dosage form for the good
release of the drug and to avoid side effects.
Particle size is an important parameter both for the
production of medicines containing particulate
solids and in the efficacy of the medicine
administration.
11. Wetting of powders
The wettability is Penetration of water into
tablets or into granules precedes dissolution.
The wettability of the powders, as measured
by the contact angle (θ) of the substance
with water
12. contact angle
• The measurement of the contact angle
gives an indication of the nature of
the surface.
• The behaviour of crystalline
materials can be related to the chemical
structure of the materials
13. Wetting of powders
• Hydrophobic drugs have dual
problems: they are not readily wetted,
and even when wetted they have low
solubility. On the other hand, because
they are lipophilic , absorption across
lipid membranes is facilitated.
14. The wetting of a solid when a liquid spreads over its
surface is referred to as spreading wetting. The
forces acting on a drop on the solid surface are
represented by Young’s equation:
γS/A = γS/L + γL/A cos θ
• where γS /A is the surface tension of the solid,
• γS /L is the solid–liquid interfacial tension,
• γL /A is the surface tension of the liquid and
• θ is the contact angle.
• The tendency for wetting is expressed by the
spreading coefficient S , as:
S = γL/A (cos θ – 1)
15. •For complete spreading of the liquid
over the solid surface, S should have a
zero or positive value.
If the contact angle is larger than 0°, the
term ( cos θ – 1) will be negative, as will
the value of S.
spontaneous wetting is thus a zero
value for the contact angle
16. Wettability and Dissolution Rate of
powders
The first step in the process of dissolution is
wetting of the dissolving surface ,which is in
contact with the dissolution medium.
The condition for complete wetting of a solid
surface is that the contact angle should be Zero.
This condition is fulfilled only when the forces of
attraction between the liquid and solid are equal
to or greater than those between liquid and
liquid.
17. Solid – Dispersion System
• Definition :
Solid dispersion is defined as dispersion
of one or more active ingredients in an
inert carrier or matrix at solid state
prepared by the melting, solvent or
melting solvent method.
19. A. Eutectic Mixtures
• When two or more substances are
mixed together they liquefy due to the
lowering of melting point than their
individual melting point. Such
substances are called as eutectic
substances.
e.g. paracetamol-urea, griseofulvin-
urea
19
20. Phase diagram (temperature versus composition)
showing boundaries between liquid and solid
phases, andthe eutectic point, E.
21. • The following factors may contribute to faster
dissolution rate of drug dispersed in the eutectic
mixtures:-
1. Increase in drug solubility.
2. Solubilization effect by the carrier which
completely dissolves in a short time in diffusion
layer surrounding drug particles.
3. Absence of aggregation and agglomeration
between fine crystallites of pure hydrophobic
drug. 21
A. Eutectic Mixtures
22. 4. Excellent wettability and dispersibility of a
drug as the encircling soluble carrier readily
dissolves and causes water to contact as wet
drug particles.
5. Crystallization of drug in a metastable
form after solidification from fused solution,
which has high solubility.
22
A. Eutectic Mixtures
23. • Eutectics are easy to prepare and
economical with no solvents involved.
The method however cannot be applied
to:
- Drugs which fail to crystallize from
mixed melt.
- Thermolabile drugs.
- Carriers such as succinic acid that
decompose at melting point. 23
A. Eutectic Mixtures
24. B. Solid Solutions
• It is made up of a solid solute dissolved in a solid
solvent. It is often called a “mixed crystal”
because the two components crystallize together in
a homogenous phase system.
• It is prepared by fusion method.
• A solid solution of poorly soluble drug in a rapidly
soluble carrier achieves a faster dissolution
because particle size of drug is reduced to
molecular size. 24
