Theories of drug dissolution

Best slides ever of theories of drug dissolution, film teory, dankwerts model, interfacial model of dissolution, noyes whitneys equation, modified noyes whitney equation, sink condition, 1st order & zero order kinetics of drug dissolution, conclution, references

1. THEORIES OF DRUG DISSOLUTION

2. Presented by……. TANMAY SAHA , TANAYA PALIT & TANUMOY GHOSH B.PHARM, 3 RD YEAR, 6 TH SEMESTER ROLL No.- 18601913099 18601913097 18601913100 GURU NANAK INSTITUTE OF PHARMACEUTICAL SCIENCE & TECHNOLOGY

3. INTRODUCTION : Drug is the single chemical entity present in a medicine that is used for diagnosis, prevention, treatment/ or cure of disease. 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. Drug dissolution mainly occurs in stomach & intestine. ENTERIC – COATED TABLETS ACIDIC DRUGS ARE USED

4. DESCRIPTION: There are many theories to explain drug dissolution. The important ones are ---- 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 / Film Theory: Simplest & most common theory of dissolution. This process of dissolution of solid particles in a liquid in absence of chemical forces, consists of two consecutive steps------ Solution of liquid to form a thin film or layer at the solid-liquid interface known as Stagnant film or diffusion layer. This layer is saturated with the drug. This step is usually rapid.

6. Diffusion of the soluble solute from the stagnant layer to bulk of the solution. This step is slower Rate – determining step in drug dissolution.

7. This theory is controlled by Noyes & Whitney equation: dC / dt = k ( C s – C b ) Where, dC / dt = dissolution rate of the drug k = dissolution rate constant ( first order ) C s = concentration of drug in the stagnant layer ( also called as the saturation or maximum drug solubility ) C b = concentration of drug in the bulk of the solution at time t.

8. Nernst & Brunner incorporated Fick’s first law of diffusion & modifies the Noyes-Whitney’s equation to: dC / dt = DAK w /o (C s - C b )/ Vh Where, D=diffusion coefficient of the drug A=surface area of the dissolving solid K w/o =water in oil partition coefficient of the drug or intrinsic dissolution rate constant. C s - C b =concentration gradient for drug of diffusion. V=volume of dissolution medium h=concentration gradient for diffusion of drug

9. Noyes-Whitney’s equation assumes that the surface area of the dissolving solid remains constants during dissolution which is practically not possible. To account for the particle size decrease & change in surface area by Hixon & Crowell’ s cubic root law of dissolution is used: W 1/3 – W 1/3 = Kt Where, W =original mass of the drug W =mass of the drug remaining to dissolve at time t K =dissolution rate constant

10. Modified Noyes & Whitney’s equation represents first order kinetics , the driving force for which is the concentration gradient (C s - C b ). To obtain good in vitro- in vivo dissolution rate correlation , in vitro- in vivo dissolution must be performed under sink condition. That means C s >> C b . dC / dt = K This equation follows Zero order kinetics. This represents that dissolution rate is constant under sink condition.

11. Danckwert’s model : Dankwert didn’t approve of existence of stagnant layer & suggested that turbulence in the dissolution medium exists at solid/liquid interface. Danckwert’s model is expressed by----------- V dC / dt = dm / dt = A( C s – C b ) Where, m=mass of solid dissolved,  

12. Interfacial barrier model : An intermediate concentration can exist at the interface as a result of solvation mechanism & is a function of solubility rather than diffusion. This concept is given by------ G = K i ( C s – C b ) Where, G=dissolution rate per unit area, K i =effective interfacial transport constant.

13. Conclusion : The diffusion layer model & Danckwert’s model were based on---- The rate-determining step that controls dissolution is the mass transport. Solid-solution equilibrium is achieved at the solid/liquid interface. The interfacial barrier model can be extendeded to both diffusion layer model & Danckwert’s model

14. References : D.M.Brahmankar & Sunil B. Jaiswal , Biopharmaceutics & Pharmacokinetics- A treatise, 2 nd Ed., Vallabh Prakashan , Absorption of Drugs, Theories of Drug Dissolution, Page no: 29 -35. V. Venkateswarlu , Biopharmaceutics & Pharmacokinetics, 2 nd Ed., Absorption of a weak acidic drug, Theories of Drug Dissolution, Page no: 33-36