theories of dissolution
TRANSCRIPT
PRESENTED BY
DEORE PRASHANT ASHOK
Department of Pharmaceutics M. Pharm. I Semester (2014-2015)
R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur .
10/10/2014 1
[email protected] Mo.09881261646
CONTENTS
Dissolution
Dissolution vs Solubility
Expression of Solubility
Drug Dissolution Process
Theories of Dissolution
References
10/10/2014 2
DISSOLUTION
Dissolution is defined as a
process in which a solid
substance solubilises in a
given solvent.
(i.e. mass transfer from
the solid surface to the
liquid phase.)
10/10/2014 3
10/10/2014 4
DISSOLUTION SOLUBILITY
Dissolution rate is defined as
the amount of solid substance
that goes into solution per
unit time under standard
conditions of temperature,
pH, solvent composition and
constant solid surface area.
Absolute solubility is defined
as the maximum amount of
solute dissolved in a given
solvent under standard
conditions of temperature ,
pressure and pH.
It is a dynamic process. It is a static process.
EXPRESSION OF SOLUBILITY
10/10/2014 5
DESCRIPTIVE TERM PARTS OF SOLVENT REQUIRED
FOR 1 PART OF SOLUTE
Very soluble Less than 1 part
Freely soluble 1 to 10 parts
Soluble 10 to 30 parts
Sparingly soluble 30 to 100 parts
Slightly soluble 100 to 1000 parts
Very slightly soluble 1000 to 10000 parts
Practically insoluble More than 10000 parts
DRUG DISSOLUTION PROCESS
10/10/2014 6
The effectiveness of a tablet in releasing the drug for
absorption depends on four steps -
1. The initial step involves the breaking of a tablet into
granules (disintegration).
2. Some times, these granules further break to yield fine
particles (deaggregation)
3. The next step involves the releasing of the drug into solution
(dissolution)
4. Absorption.
10/10/2014 7
Cont….
THEORIES OF DISSOLUTION
Three Theories:
1. Diffusion layer model / Film theory
2. Danckwert’s model / Penetration or Surface renewal theory
3. Interfacial barrier model / Double barrier or Limited
solvation theory
10/10/2014 8
1) Diffusion layer model
It involves two steps :
1. Solution of the solid to form stagnant film or diffusive layerwhich is saturated with the drug.
2. Diffusion of the soluble solute from the stagnant layer to thebulk of the solution; this is rate determining step in drugdissolution.
10/10/2014 9
The rate of dissolution is given by Noyes and Whitney:
dC/dt = k (Cs- Cb)…………(1)
where,
dC/dt = dissolution rate of the drug
k = dissolution rate constant
Cs= concentration of drug in stagnant layer
Cb= concentration of drug in the bulk of the solution at time t
10/10/2014 10
Cont….
Equation (1) was based on Fick’s second law of diffusion .
Nernst and Brunner incorporated Fick’s first law of diffusion and
modified the Noyes-Whitney’s equation to :
dC/dt = DAKw/o (Cs-Cb) …………. (2)
Vh
where,
D = diffusion coefficient of drug
A = surface area of dissolving solid
Kw/o = water/oil partition coefficient of drug
V = volume of dissolution medium
h = thickness of stagnant layer
(Cs – Cb) = conc. gradient for diffusion of drug
10/10/2014 11
Cont….
Limitation :
The Noyes-Whitney’s equation assumes that the surface area of the
dissolving solid remains constant during dissolution, which is practically not
possible for dissolving particles.
Hence, dissolution methods that involves use of constant surface area discs
are employed to determine the rate of dissolution.
To account for the particle size decreases and change in the surface area
accompanying dissolution, Hixson and Crowell’s cubic root law of
dissolution is used:
Wo1/3– W
1/3= K.t …………(3)
where,
W = mass of drug remaining to be dissolved at time t
K = dissolution rate constant
Wo = original mass of the drug
10/10/2014 12
Cont….
2) Danckwert’s model
1. Danckwert takes into account the eddies or packets that are present in the
agitated fluid which reach the solid-liquid interface, absorb the solute by
diffusion and carry it into the bulk of solution.
2. These packets get continuously replaced by new ones and expose to new
solid surface each time, thus the theory is called as surface renewal
theory.
10/10/2014 13
The Danckwert’s model is expressed by equation:
V. dC/dt= dm/dt = A ( Cs-Cb). √(γ.D)……….(4)
where,
m = mass of solid dissolved
γ = rate of surface renewal
10/10/2014 14
Cont….
3) Interfacial barrier model
The diffusion layer model and Danckwert’s model were
based on two assumptions:
1. The rate determining step that controls dissolution is the
mass transport.
2. Solid-solution equilibrium is achieved at the solid/liquid
interface. According to the interfacial barrier model, an
intermediate concentration can exist at the interface as a result
of solvation mechanism and is a function of solubility rather
than diffusion.
When considering the dissolution of a crystal, each face of
crystal will have a different interfacial barrier.
10/10/2014 15
Such a concept is given by the following equation :
G = Ki (Cs-Cb)………(5)
where,
G = dissolution rate per unit area
Ki = effective interfacial transport constant
10/10/2014 16
Cont….
REFERENCES
1. Brahmankar D.M., Jaiswal S.B. (2009), “Biopharmaceutics and
Pharmacokinetics-A Treatise” Vallabh Prakashan, 2nd Edition, Page
No. 15-48
2. Government of Indian ministry of health and family welfare (2014),
“Indian Pharmacopoeia” Indian Pharmacopoeia commission,
Ghaziabad, Volume-1, Page No. 174
3. Subrahmanyam C.V.S. (2000), “Text book of Physical Pharmaceutics”
Vallabh Prakashan, 2nd Edition, Page No. 85-105
4. Banakar U.V. (1992), “Pharmaceutical Dissolution Testing” Informa
helthcare, 1st Edition, Page No. 1-30
10/10/2014 17
Thank You
10/10/2014 18