Theories of Dissolution

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.)
Three Theories:

Diffusion layer model / Film theory

Danckwert’s model / Penetration or Surface renewal theory

Interfacial barrier model / Double barrier or Limited solvation theory

1. PRESENTED BY DEORE PRASHANT ASHOK Department of Pharmaceutics M. Pharm. I Semester (2014-2015 ) THEORIES OF DISSOLUTION R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur . 10/10/2014 1 [email protected] Mo.09881261646

2. CONTENTS Dissolution Dissolution vs Solubility Expression of Solubility Drug Dissolution Process Theories of Dissolution References 10/10/2014 2

3. 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

4. 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.

5. 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

6. DRUG DISSOLUTION PROCESS 10/10/2014 6

7. The effectiveness of a tablet in releasing the drug for absorption depends on four steps - The initial step involves the breaking of a tablet into granules (disintegration). Some times, these granules further break to yield fine particles (deaggregation) The next step involves the releasing of the drug into solution (dissolution) Absorption. 10/10/2014 7 Cont….

8. THEORIES OF DISSOLUTION Three Theories: Diffusion layer model / Film theory Danckwert’s model / Penetration or Surface renewal theory Interfacial barrier model / Double barrier or Limited solvation theory 10/10/2014 8

9. 1) Diffusion layer model It involves two steps : Solution of the solid to form stagnant film or diffusive layer which is saturated with the drug. Diffusion of the soluble solute from the stagnant layer to the bulk of the solution; this is rate determining step in drug dissolution. 10/10/2014 9

10. The rate of dissolution is given by Noyes and Whitney: dC / dt = k (C s - C b )…………(1) where, dC / dt = dissolution rate of the drug k = dissolution rate constant C s = concentration of drug in stagnant layer C b = concentration of drug in the bulk of the solution at time t 10/10/2014 10 Cont….

11. 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 = DAK w/o (C s -C b ) …………. (2) Vh where, D = diffusion coefficient of drug A = surface area of dissolving solid K w/o = water/oil partition coefficient of drug V = volume of dissolution medium h = thickness of stagnant layer (C s – C b ) = conc. gradient for diffusion of drug 10/10/2014 11 Cont….

12. 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: W o 1/3 – W 1/3 = K.t …………(3) where, W = mass of drug remaining to be dissolved at time t K = dissolution rate constant W o = original mass of the drug 10/10/2014 12 Cont….

13. 2) Danckwert’s model 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. 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

14. The Danckwert’s model is expressed by equation: V. dC/ dt = dm/ dt = A ( C s - C b ). √( γ .D)……….(4) where, m = mass of solid dissolved γ = rate of surface renewal 10/10/2014 14 Cont….

15. 3) Interfacial barrier model The diffusion layer model and Danckwert’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 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

16. Such a concept is given by the following equation : G = K i (C s - C b )………(5) where, G = dissolution rate per unit area K i = effective interfacial transport constant 10/10/2014 16 Cont….

17. REFERENCES Brahmankar D.M., Jaiswal S.B. (2009), “ Biopharmaceutics and Pharmacokinetics-A Treatise ” Vallabh Prakashan, 2 nd Edition, Page No. 15-48 Government of Indian ministry of health and family welfare (2014), “ Indian Pharmacopoeia ” Indian Pharmacopoeia commission, Ghaziabad, Volume-1, Page No. 174 Subrahmanyam C.V.S. (2000), “ Text book of Physical Pharmaceutics ” Vallabh Prakashan, 2 nd Edition, Page No. 85-105 Banakar U.V. (1992), “ Pharmaceutical Dissolution Testing ” Informa helthcare, 1 st Edition, Page No. 1-30 1 0/10/2014 17

18. Thank You 10/10/2014 18