A detail introduction and notes on Dissolution Models, Methods, Factors and Kinetics.

1. Dissolution Models and
Methods
Factors and Kinetics..
By:- Siddharth Kumar Sahu
M. Pharmacy

2. Questions
• Q.1. write in detail about the various method of dissolution
testing? (20)
• Q.2. define dissolution. Discuss dissolution of drug from
solid dosage form. Write various modern methods for
testing of dissolution. (20)
• Q.3. discuss in detail various official & non-official models
for testing dissolution rate? (20)
• Q.4. Discuss factors affecting dissolution of drug. Describe
dissolution kinetics. (20)

3. Content
• Introduction
• Theories of Dissolution
• Invitro Dissolution Test Models
• Factors Affecting Dissolution
• Kinetics of Dissolution.

4. Introduction
Dissolution is a process in which a solid substance is solubilised
in a given solvent i.e., mass transfer from solid surface to liquid
phase.
(or)
It is a process by which drug released from solid dosage form
and immediately goes into molecular solution.
Rate of dissolution is the amount of drug substance that goes in
solution per unit time under standardized conditions of
liquid/solid interface, temperature and solvent composition.
It is a Rate Determining Step
If the drug is hydrophilic with high aqueous solubility then
dissolution is rapid and rate determining step

5. Theories of Dissolution

6. 1. Diffusion Layer Model/ Film theory
• Solution of the solid to form a thin layer at the solid/liq. interface is
called Stagnant film or Diffusion layer which is with saturated drug.
• Soluble solute form diffuses from the stagnant layer to the bulk of the
solution. This step is slower and rate-determining step in drug
dissolution.
• This rate of dissolution if the process is diffusion controlled and
involves no chemical reaction. It can be explained by Noyes –
Whitney Equation .
𝐝𝐂
𝐝𝐭
=
𝐤(𝐂 𝐬−𝐂 𝐛)
𝐕𝐡
where
dC/dt = dissolution rate of drug
Cs = conc. Of drug in stagnant layer
Cb= conc. Of drug in bulk of the solution at time t.
k = dissolution rate constant. (First order)

7. 1.Diffusion Layer Model/ Film theory

8. 2. Danckwert’s Model
• This model suggest that turbulence in
dissolution medium exists at the
solid/liquid interface.
• This theory is also called as Surface
Renewal Theory.
V
𝑑𝐶
dt
𝑑𝑚
𝑑𝑡
= 𝐴(𝐶𝑠 − 𝐶𝑏) 𝛾𝐷
• m = mass of solid dissolution,
• 𝛾 = rate of interfacial tension,
• D = diffusion coefficient of the drug

9. 3. Interfacial Barrier Model
• This model considers the phenomenon of drug dissolution as crystal dissolution.
The solid gets hydrated initially.
• a different interfacial barrier such a concept is given by the following equation..
G = Ki (cs - cb)
where
G = dissolution rate per unit area. g/cm², min
Ki = effective interfacial transport constant, min⁻¹
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 diffusivity D may not be independent of saturation
concentration cs. Therefore the interfacial model
can be extended to both diffusion layer model and Danckwerts model.

10.  Factors Influencing Dissolution
a) Factors related to Physicochemical Properties
of Drug
b) Factors related to Drug Product Formulation
c) Processing Factor
d) Factors Relating Dissolution Apparatus
e) Factors Relating Dissolution Test Parameters

11. a.) Factors related to Physicochemical Properties
of Drug
1. DRUG SOLUBILITY
Minimum aqueous solubility of 1% is required to avoid potential solubility limited
absorption problems.
2. SALT FORMATION
Surface area increases with decrease in particle size, higher dissolution rates may be
achieved through reduction of particle size.
3. PARTICLE SIZE
Since, surface area increases with decrease in particle size, higher dissolution rates
may be achieved through reduction of particle size. Direct relates to surface area
and dissolution rate.
4. SOLID STATE CHARACTERISTICS
Anhydrous forms dissolve faster than hydrated form because they are
thermodynamically more active than hydrates.
Amorphous forms of drug tend to dissolve faster than crystalline materials.

12. b.) Factors related to Drug Product Formulation
1. DILUENTS
particles form a layer on the outer surface of hydrophobic drug
particles resulting in imparting hydrophilic character to granules &
thus increase in effective surface area & rate of dissolution.
2. DISINTEGRANTS
3. BINDERS AND GRANULATING AGENTS
Large amt. of binder increase hardness & decrease disintegration
/dissolution rate of tablet.
4. METHOD OF GRANULATION
5. COMPRESSION FORCE

13. c.) Factors Relating Dissolution Apparatus
 Agitation
d.) Factors Relating Dissolution Test Parameters
 Temprature
 Dissolution medium
 pH

14. OFFICIAL METHODS
&
UN-OFFICIAL METHODS
IN-VITRO DISSOLUTION TESTING MODELS

15. Type I.P. USP B.P. E.P.
Type 1
Paddle
apparatus
Basket
apparatus
Basket
apparatus
Paddle
apparatus
Type 2
Basket
apparatus
Paddle
apparatus
Paddle
apparatus
Basket
apparatus
Type 3
Reciprocating
cylinder
Flow through
cell apparatus
Flow through
cell apparatus
Type 4
Flow through
cell apparatus
Type 5
Paddle over
disk
Type 6
Rotating
cylinder
Type 7
Reciprocating
disk
Official Dissolution Apparatus

16. Unofficial Methods
• 1. Rotating Disk Methods
• 2. Beaker Method
• 3. Flask Stirrer Method
• 4. Peristaltic Method
• 5. Rotating Bottle Method
• 6. Dialysis Method
• 7. Diffusion Cell.

17. APPARATUS-1 (ROTATING BASKET)
DESIGN:
Vessel: -Made of borosilicate glass.
-Semi hemispherical bottom
-Capacity 1000ml
Shaft : -Stainless steel 316
-Rotates smoothly without
significance wobble(100 rpm)
-Speed regulator
Water bath:-Maintained at 37±0.5ºC
USE: Tablets, capsules, delayed release
suppositories, floating dosage forms.
OFFICIAL METHODS:-

18. APPARATUS-2 (PADDLE)
DESIGN:
Vessel: -Same as basket apparatus
Shaft: -The blade passes through the shaft so that
the bottom of the blade fuses with bottom of the shaft.
Stirring elements: -Made of Teflon
For laboratory purpose
-Stainless steel 316
Water-bath:- Maintains at 37±0.5°C
Sinkers:- Platinum wire used to prevent
tablet/capsule from floating
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Automated Dissolution System.mp4
video managerERWEKA Offline
System Overview.mp4

19. APPARATUS-3 (RECIPROCATING CYLINDER)
DESIGN:
Vessel: -Set of cylindrical flat bottom glass vessels
-Set of reciprocating cylinders
-stainless steel fittings(type 316) and
screens made of non-sorbing or
non-reactive materials.
Agitation type: -Reciprocating
-5-35 rpm
Volume of dissolution medium:-200-250ml
Water bath:- Maintain at 37±0.5°C
USE: Tablets, beads, controlled and
extended release formulations

20. APPARATUS-4 (FLOW THROUGH CELL)
DESIGN:
Reservoir : -For dissolution medium
Pump : -Forces dissolution medium through cell
-Holding a sample
-Flow rate 10-100ml/min
-Laminar flow is maintained
-Peristaltic/centrifugal pumps
are not recommended
Water bath:- Maintain at 37±0.5°C
USE:
Low solubility drugs, micro particulates,
implants, suppositories, controlled release
formulations

21. APPARATUS-5 (PADDLE-OVER-DISK)
DESIGN:
Vessel
Shaft
Stirring elements- rotating speed 25-50 rpm
Sample holder:-disk assembly that hold a product in such a way
that release surface is parallel with paddle
-Paddle is directly attached over disk assembly
-Samples are drawn between surface off the
medium and top of the paddle blade
Volume:900ml
Temperature:32°C

22. APPARATUS-5 (PADDLE-OVER-DISK)

23. APPARATUS-6 (ROTATING CYLINDER)
DESIGN:
Vessel:- In place of basket, cylinder is used.
Shaft :-Stainless steel 316
Sample :- Mounted to cuprophan (inner porous
cellulosic material)
- An entire system adheres to cylinder.
- Dosage unit is placed in cylinder and
release from side out.
Water-bath: maintained at 32±0.5°C
USE:
Transdermal patches cannot be cut into small size.
Solid dosage forms, pH profile , small volumes

24. APPARATUS-7 (RECIPROCATING-DISK)
DESIGN:
Vessel:-Flat bottomed cylindrical vessel
-Volume of dissolution medium
Shaft :
Sample : -Placed on disk shaped holders
Agitation :-Reciprocation
-Reciprocating frequency 30 cycle/sec
Water-bath:-Maintain at 32±0.5°C
USE:
Transdermal patches
constant temp water bath
disk
dissolution
medium
shaft

25. • 1. ROTATING/STATIC
DISK METHOD
In this method ,the drug
is compressed in a non-
disintegrating disc
without excipients.
The disc is mounted in a
holder so that only one
face of the disc is
exposed to the dissolution
medium.
• 2. BEAKER METHOD:
Dissolution medium, 250ml of
0.1N HCl at 37°C placed in a
400ml beaker.
Agitation by three blade
polyethylene stirrer,5cm
diameter and rotates at 60 rpm.
Stirrer immersed to a depth of
2.7 cm in medium and in the
center.
UNOFFICIAL METHODS

26. 3.PERISTALSIS METHOD:
To stimulate hydrodynamic condition of GIT tract in an in-vitro
dissolution device.
Dissolution medium is pumped with peristaltic action through the
dosage form.
4.DIALYSIS METHOD:
Cell consist of 32mm inflated membrane.
The cell suspended , from the arm of the tablet disintegration
apparatus and containing the dosage form in
150ml of distilled water at 37°C.
Agitation by slight flexing and stretching
of the dialysis membrane as it enters and
Leaves. The bath. Rotated at 60rpm.
.

27. KINETICS OF DISSOLUTION
KINETICS FEATURE GRAPH PLOTTED
ZERO-ORDER Drug release rate is independent
of concentration of dissolved
substance
Qt = Q₀ + k₀t
Cumulative % of drug
release v/s time (hr.)
Straight line comes
FIRST- ORDER Rate is depends on
concentration of dissolve
substance.
log 𝑄𝑡 = log Q₀ +
𝑘𝑡
2.303
Log cumulative % of drug
remains to be dissolved v/s
time (hr.)
Straight line comes

28. •
KINETICS FEATURE GRAPH PLOTTED
HIGUCHI- MODEL
Describes the release
by dissolution and
change in surface area
and diameter of
dissolved particles.
Q = KH t½
Initial concentration -
%drug remaining v/s
time (hr.)
Straight line comes
HIXON-CROWEL Its suggest drug release
by diffusion
mechanism.
𝐾ℎ𝑐𝑡 = 𝑄₀1/3− 𝑄𝑡1/3
Cumulative % of drug
release v/s square root
of time (hr.)
Straight line comes
KORSMEYER-
PEPPAS
[Mt/M] = Kn t⁰ Log cumulative % of
drug remaining to be
dissolve v/s log time
(hr.)
Straight line comes

29. Dissolution rate under sink
condition follow zero order
dissolution rate.
First order under non sink condition
Zero order dissolution
Under sink condition
Time
Conc.ofdissolvedrug

30. References
• D.M. Brahmankar, “Bio-pharmaceutics And
Pharmacokinetics - A Treatise”, Vallabh
Prakashan, Page No. 20–31.
• Leon Shargel, “Applied Bio-pharmaceutics &
Pharmacokinetics”, 4th Edition, Page No. 132-136.
• www.slideshare.com
 Roja Thoguta, Factors Effecting Dissolution &
Dissolution Testing.
 Nilesh S. Jawalkar, Dissolution:-a Heart of
Pharmaceutics.
 Mohammed Ameer Ahmed, Invitro Dissolution Testing

32. IN-VITRO DISSOLUTION TESTING MODELS
• 1) NATURAL CONVECTION NON SINK METHODS:
a) Klein solveigmeter method
b) Nelson hanging pellet method
c) Levy static disk method
• 2) FORCED CONVECTION NON SINK METHODS:
a) Tumbling method
b) Levy or Beaker method
c) Rotating disk method
d) Particle size method
 e) USP Rotating basket apparatus
 f) USP Paddle apparatus
A. Non-sink Methods

33. B. Sink Methods
• 3) FORCED CONVECTION SINK DEVICES:
a) Wurster pollis adsorption method
b) Partition method
c) Dialysis method
d) Rotating disk apparatus
• 4) CONTINOUS FLOW/FLOW THROUGH METHODS:
a) Pernarowski method
b) Langen bucher method
c) Baun and Walker
d) Tingstad and Reigelman
e) Modified column apparatus
f) Takenaka method