1. Dissolution Theory
By
Dr.Chandra Sekhar Patro
Raghu College of Pharmacy
Visakhapatnam
2. Definition-
• Dissolution is a process in which a solid substance
becomes dissolved in a given solvent i.e. transfer of
solute from the solid surface to the liquid phase.
• 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.
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3. Suspension Fine particles ………………Aggregates Tablets/Capsules
Dissolution
Solution Drug in Solution Absorption
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4. Theories of Drug Dissolution
I. Diffusion layer model/Film Theory
I. Interfacial barrier model/Double barrier or Limited
solvation theory.
II. Danckwert’s model/Penetration or surface renewal
Theory
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6. This model assessed by Noyes whitney equation.The
assumptions are
Drug particles – spherical and equal in size.
Dissolution process controlled by diffusion of molecules
No chemical reaction between drug and solvent particles
Thickness of diffusion layer and solubility of drug in diffusion
layer are constant
It involves two steps :-
1. Solution of the solid to form stagnant film or diffusive layer
which is saturated with the drug
2. Diffusion of the soluble solute from the stagnant layer to
the bulk of the solution
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7. The rate of dissolution is given by Noyes and
Whitney:
Rate of dissolution dm = DA(Cs- Cg)
dt h
Where,
dm/dt= dissolution rate of the drug
D= diffusion coefficient
Cs= concentration of drug in stagnant layer
Cg= concentration of drug in the bulk of the
solution at time t
(Cs- Cg) = concentration gradient
The above equation states that it is a first order
process. 7
8. •This is true for in-vitro dissolution which is
characterized by non-sink conditions.
•The in-vivo dissolution is rapid as sink conditions are
maintained by absorption of drug in systemic
circulation i.e. Cg=0 and rate of dissolution is
maximum.
Under sink conditions, if the volume and surface area
of the solid are kept constant, then
dc = K
dt
This represents that the dissolution rate is constant
under sink conditions and follows zero order kinetics.
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9. In this process at the surface of solid particles,forming a
saturated solution around the particles
The dissolved particles in saturated solution known as
stagnant layer diffuses to the bulkof the solvent from higher
concentration to lower concentration.
Hoxon and Cowell’s root law of dissolution is
W01/3 - Wt1/3 =K.t
Where W0 = Original mass of drug.
Wt = Mass of drug removed at t.
10. Dissolution rate under non-sink and sink conditions.
zero order dissolution
under sink condition
first order dissolution under
Conc. of dissolved drug
non-sink condition
Time
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11. II. Danckwert’s model/Penetration or surface
renewal Theory :-
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12. • The turbulence present in the dissolution medium
causes rapid movement of solvent packets in ramdom
manner.
• So the drug concentration in them never reaches Cs.
• So dm =S1/2 . D1/2 (Cs-Cg)
Where S=Mean rate at which fresh surface is produced.
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13. III. Interfacial barrier model/Double barrier or Limited solvation
theory
• According to the interfacial barrier model, an intermediate
concentration can exist at the interface as a result of solvation
mechanism and is function of solubility. When considering dissolution
of crystal, each face of the crystal will have the different interfacial
barrier.
• For solubility of a solid high free energy of activation required -
So it is not instaneous.
• Rate of solubility of a solid in liquid becomes rate limiting rater
than diffusion of dissolved molecules.
The concept of this theory is explained by following equation-
dm/dt = Ki (Cs - Cb)
Where
Ki = effective interfacial transport rate constant.
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14. REFERENCES
Industrial pharmacy BY Lacchmann Liebermann
Umesh v. banakar ,pharmaceutical dissolution testing, volume
47,marcel dekkar, inc., new york,410-450.
Brahmankar D.M., Jaiswal, Biopharmaceutics and
pharmacokinetics, 1997, Vallabh prakashan, Delhi,290-292.
Leon Shargel, Applied Biopharmaceutics &
Pharmacokinetics; 4th edition, page no. 132-136
Text book of Biopharmaceutics and pharmacokinetics, by
Shobha Rani R. Hiremath.
D.M.Brahmankar, Biopharmaceutics and pharmacokinetics- A
Treatise; Vallabh Prakashan, page no. 20–31.
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15. United States Pharmacopoeia – 24, page no.: 1942 – 1951.
Alton’s pharmaceutics “ The design and manufacturing of
medicines”, by Michael E. Alton, page no.: 21 – 22.
Principle and application of Biopharmaceutics and
Pharmacokinetics, by Dr. H.P. Tipnis, Dr. Amrita Bajaj.
Remington, The Science and Practice of Pharmacy,21st edition,
Voulme 1.
www.google.co.in
www.dissolution.com
www.usp.org
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