DISSOLUTION, THEORIES OF DRUG DISSOLUTION, DIFFUSION LAYER MODEL, NYOES WHITNEY EQUATION, FACTORS INFLUENCING DISSOLUTION AND DISSOLUTION STUDIES, DISSOLUTION APPARATUS, USP Type, IP Type INVIVO INVITRO CORRELATION

1. DISSOLUTION
Presented By,
Harsh Kumar Pandey (21MPI1003)
M.Pharma (Industrial Pharmacy)
Pharmaceutical formulation Development ( PHT 642)
1st Sem (Chandigarh University, UIPS)

2. CONTENT
 Dissolution
 Rate of dissolution
 Process of dissolution
 Theories of dissolution
 Factor influencing dissolution
 Types of dissolution apparatus
 In vitro-In vivo correlation

3. DISSOLUTION
Definition- Dissolution is a process in which a solid substance solubilizes in a given solvent i.e. mass transfer from the solid
surface to the liquid phase.
Rate of Dissolution- It is the amount of drug substance that goes in solution per unit time under standardized conditions of
liquid/solid interface, temperature and solvent composition.
Process of Dissolution
Schematic-representation-of-tablet-dissolution-processes--p3owz4o547o379sorn38lljdxqe8dyo0el348as52a

4. Theories of Drug Dissolution
 Diffusion layer model/Film Theory
 Danckwert’s model/Penetration or surface renewal Theory
 Interfacial barrier model/Double barrier or Limited solvation theory

5. Diffusion Layer Model
• It is Also called ‘film theory’.
• Formation of a thin film at the interface, called as stagnant layer.
• Two steps are involved:
1) Interaction of solvent with drug surface to form a saturated drug layer , called stagnant layer.
2) Diffusion of drug molecules from stagnant layer into bulk of the system.
source-
https://www.google.com/url?sa=i&url=http%3A%2F%2Fwww.pharmacy180.com%2Farticle
%2Fphysicochemical-factors-affecting-drug-absorption

6. Noyes-Whitney’s Equation
The rate of dissolution is given by Noyes and Whitney:
𝑑𝑐
𝑑𝑡
= k (Cs- Cb)
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

7. Modified Noyes-Whitney’s Equation
𝑑𝑐
𝑑𝑡
=
DAKw/o (Cs – Cb )
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.

8. Danckwert’s Model/Penetration or Surface Renewal Theory
• Dankwert 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
• 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
Source-
https://www.google.com/url?sa=i&url=https%3A%2F%2Fslideplayer.com
Screenshot of dissolution presentation from slideshare.com by mohanto

9. Interfacial Barrier Model/Double Barrier Or Limited Solvation Theory
The Diffusion layer model and the Dankwert’s model were based on two assumptions:
• The rate determining step that controls dissolution is the mass transport.
• Solid solution equilibrium is achieved at the solid/liquid interface.
• According to interfacial barrier model, an intermediate conc. 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 the crystal will have a different interfacial barrier given by following equation,
G = ki (Cs – Cb)
Where , G = dissolution per unit area
Ki = effective interfacial transport constant In this theory
• The interfacial barrier model can be extended to both Diffusion layer model and the Dankwert’s model.

10. FACTORS INFLUENCING DISSOLUTION AND DISSOLUTION STUDIES
1. Physicochemical Properties of Drug
2. Factors Relating Dissolution Apparatus
3. Factors Relating Dissolution media
PHYSICOCHEMICAL PROPERTIES OF DRUG
• Drug solubility
• Particle size
• Salt formation
• Solvates and hydrates
• pH effect
• Adsorbents
• Polymorphism and amorphism
• Co-precipitation
• Complexation

11. FACTORS RELATED TO THE APPARATUS
• Size and shape
• Stirring device
• Vibrations
• Alignment of the stirring elements
• Temperature
FACTORS RELATED TO DISSOLUTION MEDIA
• pH of dissolution media
• Surface tension
• Viscosity
• Nature of medium

12. DISSOLUTION TESTING
• Dissolution and drug release tests are in-vitro tests that measure the rate and extent of dissolution or
release of the drug substance from a drug product, usually aq. medium under specified conditions.
• It is an important QC procedure for the drug product and linked to product performance in-vivo.
NEED FOR DISSOLUTION TESTING:
• Evaluation of bioavailability.
• Batch to batch drug release uniformity.
• Development of more efficacious and therapeutically optical dosage forms.
• Ensures quality and stability of the product.
• Product development, quality control, research and application.

13. https://www.google.com/url?sa=i&url=https%3A%2F%2Fchrominfo.blogspot.com%2F2018%2F07%2Fdifferent-types-of-
dissolution.html&psig=AOvVaw0ja9iWOs3ik9jbXMQ3szH4&ust=1640971476622000&source=images&cd=vfe&ved=0CAsQjRxqFwoTCLDEjqqFjPUCFQAAAAAdAAAAABA
D

14. .
https://www.google.com/imgres?imgurl=https%3A%2F%2Fwww.pharmapproach.com%2Fwp-content%2Fuploads%2F2018%2F09%2FComparison-of-different-USP-dissolution-
apparatuses.

15. IN VITRO-IN VIVO CORRELATIONS OF DISSOLUTION
Dissolution method provide a convenient means of testing a drug product, when a proper dissolution method is chosen the
rate of dissolution of the product may be correlated to rate of absorption of drug in the body.
Screenshot of textbook of physical pharmaceutics by CV Subramanyam

16. REFERENCE
• CVS Subrahmanyam “Textbook of Physical Pharmaceutics” Vallabh Prakashan, Delhi.
• https://www.researchgate.net/publication/318462831_Dissolution
• https://www.pharmpress.com/files/docs/remington-education-physical-pharmacy-sample-chapter-3.pdf
• https://en.wikipedia.org/wiki/Dissolution
• https://www.uspnf.com/sites/default/files/usp_pdf/EN/USPNF/revisions/m99470-gc_711.pdf