1. Biopharmaceutics 4th year

2. Dissolution and release of drug from gastrointestinal tract (in vivo and in vitro)

3. Theories of Dissolution
Dissolution is a process in which a solid substance solubilizes in a given solvent. i.e mass transfer from a solid surface to liquid phase.

4. Theories of Dissolution
Some of important theories are:
Diffusion layer model/ film theory
Dankwert’s model/ penetration or surface renewal theory
Interfacial barrier model/double barrier or limited solvation theory

5. Diffusion layer model/ Film theory
Is simplest and most common theory of dissolution
Is the process of dissolution of solid particles in liquid, in the absence of chemical forces

6. Diffusion layer model/ Film theory
Consist of two consecutive steps:
Solution of the solid to form a thin film or layer at the solid/liquid interface called stagnant film or diffusion layer which is saturated with the drug.
This step is rapid

7. Diffusion layer model/ Film theory
Consist of two consecutive steps:
2. Diffusion of the soluble solute from the stagnant layer to the bulk of the solution
This step is slower

8. Diffusion layer model/ Film theory

9. Diffusion layer model/ Film theory
D = diffusion coefficient of drug A = surface area of dissolving drug Kw/o = partition coefficient of drug Cs- Cb = concentration gradient V = volume of dissolution medium h = thickness of stagnant layer

10. Diffusion layer model/ Film theory
The equation that explain the rate of dissolution when the process is diffusion controlled is

11. Influence of some parameters on dissolution rate of drug
Diffusion coefficient D
Greater value faster dissolution
Diffusion decrease as viscosity of the dissolution medium increase

12. Influence of some parameters on dissolution rate of drug
2) Surface area A
Greater surface area faster dissolution
Can be increased by micronization of drug particles

13. Influence of some parameters on dissolution rate of drug
3) Water/oil partition coefficient Kw/o
Higher value , more hydrophilicity , faster dissolution .

14. Influence of some parameters on dissolution rate of drug
4) Concentration gradient Cs- Cb
Greater the concentration gradient , faster diffusion and dissolution
Can be increased by increasing drug solubility and volume of the dissolution medium

15. Influence of some parameters on dissolution rate of drug
5) Thickness of the stagnant layer
Increase thickness, lesser diffusion and dissolution
Can be decreased by agitation

16. Diffusion layer model/ Film theory
The in vivo dissolution is always rapid than in vitro dissolution ??
The moment the drug dissolves, it absorbed into systemic circulations Cb = 0
Under in vivo condition there is no concentration build up in the bulk Cs >> Cb
The dissolution will be at maximum
sink conditions are maintained

17. Diffusion layer model/ Film theory
In case of in vitro dissolution, after sometime the dissolution slows down due to build up in the concentration of drug in the bulk of the solution
So it under non sink condition

18. Bathing the dissolving solid with fresh solvent from time to time
To obtain good in vitro – in vivo dissolution rate correlation, the in vitro dissolution rate must be carried under sink condition:
Bathing the dissolving solid with fresh solvent from time to time
Increase the volume of dissolution fluid
Removing of the dissolved drug
Adding water miscible solvent such as alcohol
Adding adsorbent to remove dissolved drug

19. Danckwert’s Model (Penetration or Surface Renewal Theory)
Suggest that turbulence in the dissolution medium exists at the solid/liquid interface.
The agitated fluid consisting of macroscopic mass of eddies or packets reach the solid/liquid interface at random fashion due to eddy currents
Absorb the solute by diffusion and carry it to the bulk of the solution

20. Danckwert’s Model (Penetration or Surface Renewal Theory)
Packets are continuously replaced by new packets from fresh solvent
Drug concentration at solid/liquid interface never reaches Cs and has lower limit of Ci

21. Danckwert’s Model (Penetration or Surface Renewal Theory)
Danckwert’s Model is expressed by equation M = mass of solid dissolving Ɣ = rate of surface renewal

22. Danckwert’s Model (Penetration or Surface Renewal Theory)

23. Interfacial Barrier Mode
According to this model, an intermediate concentration is exist at interface as a result of solvation mechanism
This model expressed by
G = dissolution rate per unit area
Ki = effective interfacial constant

24. In vitro Dissolution Test
In the pharmaceutical industry, in vitro dissolution is one of the most important physicochemical tests of drug products.
In general there are many dissolution apparatus. Apparatus I (rotating basket) and
Apparatus II (rotating paddle) are the most commonly used for oral dosage forms.

25. Factors considered in the design of dissolution test”
Factors relating to the dissolution apparatus:
Size and shape of container, nature and speed of
agitation, performance precision of apparatus.
2. Factors relating to the dissolution fluid:
Composition (water, 0.1N HCL, buffer,..),
volume, temperature (37Cº)

26. Factors considered in the design of dissolution test”
3. Process parameters: Methods of introduction of dosage form, sampling techniques, changing the dissolution medium

27. Rotating Basket Apparatus (Apparatus 1)
Consist of:
beaker having semispherical bottom
with 1 L capacity
Immersed in a water bath to maintain the
temperature 37Cº
Basket of 22 mesh located 2 cm distance
from bottom rotated through a shaft

28. Rotating Paddle Apparatus (Apparatus 2)
It is the same as Apparatus 1 except the basket is replaced by paddle
Dosage form is allowed to sink at the vessel bottom.

29. In vitro Dissolution Test

30. In vitro – In Vivo Correlation

31. In vitro – In Vivo Correlation
there has been increased investigation and success in using in vitro tests to evaluate or predict in vivo performance of solid drug product FDA defines IVIVC as “A predictive mathematical model describing the relationship between an in vitro property of a dosage form (usually the rate or extent of drug dissolution or release) and a relevant in vivo response

32. Objective To ensure batch to batch consistency of a drug product
To serve as a tool for development of a new dosage form

33. In Vitro – In Vivo Correlation
Correlation Based on the Plasma Level Data
Correlation Based on the Urinary Excretion Data
Correlation Based on Pharmacologic Response