This document discusses dissolution, which refers to the process by which a solid drug product dissolves into solution. It describes the film theory of dissolution, where a saturated film forms at the solid-liquid interface and drug diffusion through this film is the rate-determining step. Factors that affect dissolution are also outlined, including drug properties like solubility and particle size, as well as dosage form properties and test parameters. Equations for describing dissolution kinetics like the Noyes-Whitney and Hixson-Crowell cube root models are provided. Intrinsic dissolution rate, which measures dissolution under standardized conditions, is also defined.

1. Dissolution
(Dr.) Mirza Salman Baig
Assistant Professor (Pharmaceutics)
AIKTC, School of Pharmacy,New Panvel
Affiliated to University of Mumbai (INDIA)

2. Dissolution
• Dissolution refer to the processes by
which a solid phase (tablet or
powder) goes into solution (water)
• Drug release is processes by which a
drug leaves a drug product and is
subjected to ADME and available for
pharmacological action

3. Dissolution Mechanism
(Film Theory of dissolution)
• Solution of the solid form a thin film or
layer at the solid / liquid interface called as
stagnant film or diffusion layer which
is saturated with the drug this step is
usually rapid (instantaneous).
• Diffusion of the soluble solute from the
stagnant layer to the bulk of the solution
this step is slower and is therefore the
rate determining step in the
drugdissolution.

4. Dissolution Mechanism

5. Dissolutionn from solid
dosageform (Tablet)

6. Noys Whitney Equation
Rate at which solid dissolve in solvent
• dM/dt = DS/h . (Cs-C)
Ø where, M= mass of solute dissolved in time t
Ø dM/dt = mass rate of dissolution
Ø D= Diffusion coeff
Ø S= surface area of exposed solid
Ø h= Thickness of diffusion layer
Ø Cs= solubility of solute
Ø C= concentration of solute at time t
Ø K= D/h
• dM/dt = KS (Cs-C)

7. Factors affecting dissolution
• Factors related to physicochemical
properties of drug
– Solubility
•Maximum amount of solute that can be
dissolved in given amount of solvent
– Particle size
•Dissolution rate is directly proportional
to specific surface area of drug
– Polymorphism
•Amorphous solid dissolve faster compare
to crystalline

8. Factors affecting dissolution
• Factors related to dosageform
(formulation)
• Granulating agent
– Gelatin provide faster dissolution rate to
barbital tablet as it impart hydrophilic
character to drug
• Disintegrant & Diluent
– Increase in starch concentration from 5% to
20% increased dissolution 3 times faster in
salicylic acid tablets
• Lubricant
– If granules are hydrophobic then hydrophilic
lubricant will enhance dissolution

9. Factors affecting dissolution
• Factors related to dissolution test
parameters
• Temperature
– As temperature increases rate of dissolution
increases
• Agitation
– If rate of agitation increases then thickness of
diffusion layer decreases and dissolution will
be faster
• Dissolution medium (pH)
– 0.1N HCl to simulate gastric condition

10. Dissolution test appratus
(Paddle/USP Dissolution test appratus-2)

11. Dissolution test appratus
(Basket/ USP Dissolution test appratus-1)

12. Measurement of dissolution rate
(USP Dissolution test appratus-1 or Basket)
• In this method 40 mesh basket is rotated at 25 to
150 rpm.
• Dosage unit (tablet) is placed inside basket
• It is immersed in 900ml of dissolution test medium
• Aliquot (sample) of 5-10 ml withdrawn at regulat
time interwal (5-10 min) and equal amount of
dissolution medium is restored in DT apparatus
• UV absorbance is noted for each sample (at λmax of
drug)
• Concentration of drug in each sample is
determined using calibration plot.
• Dissolution graph can be plotted Conc vs Time

13. Calibration curve

14. Dissolution graph

16. Dissolution Rate
• The rate of dissolution of chemical
(drug) from solid state is defined as
the amount of drug substance that
goes into solution per unit time under
standardized condition of liquid/solid
interface, temperature and solvent
composition.

17. Intrinsic Dissolution Rate
• The rate of dissolution of pure API
when conditions such as surface area,
temperature, agitation, pH, ionic
strength of dissolution medium is
kept constant is known as intrensic
dissolution.

18. Intrinsic Dissolution Rate
• Mathematically intrinsic dissolution rate
can be expressed by Noys Whitney
equation
• dM/dt = KS (Cs-C)
• dM/dt = mass rate of dissolution
• K= Diffusion coeff / Thickness of diffusion layer, K=D/h
• S= surface area of exposed solid
• Cs= solubility of solute
• C= concentration of solute at time t

19. Hixson – Crowell Cube root Law
Dosageform's dimentions reduses proportionally but
geometric shape remain constant
Hixon Crowell cube root equation for dissolution
kinetics is based on assumption that:
a) Dissolution occurs in plane parallel to dosage
form surface
b) Agitation is uniform all over the exposed surfaces
and there is no stagnation
c) The particle of solute retains its geometric shape

20. Hixson – Crowell Cube root Law
• The particle (sphere) has radius r and surface area 4Π r2
• Through dissolution the radius is reduced by dr and the
infinitesimal volume of section lost is
• dV = 4Π r2 . dr ------------------(1)
• For N such particles, the volume loss is
• dV = 4N Π r2 . dr ----------------------------(2)
• The surface of N particles is
• S = 4 N Π r2 -----------------------------(3)
• Now ,the infinitesimal mass change as represented by he
Noyes-Whitney equation is
• -dM = k.S.Cs.dt ---------------------------(4)... (k=D/h)

21. • The drugs density is multiplied by the infinitesimal volume change .....
ρ.dV = dM....from eqn (4)
• -ρ.dV = k.S.Cs.dt --------------------------- (5)
• Equations (2) and (3) are substituted into equation (5) , to yield
• -4 ρ N Π r2 . dr = 4 N Π r2 . k .Cs .dt -------------(6)
• Equation (6) is divided through by 4 N Π r2 to give
• - ρ . dr = k Cs.dt -------------------------(7)
• Integration with r = ro at t= 0 produces the expression
• r = ro – (kCs . t/ ρ) -----------------------------(8)
• The radius of spherical particles can be replaced by the mass of N
particles by using the relationship of volume of sphere
• M = N ρ(Π/6)d3 ----------------------------(9)
• Taking cube root of the equation (9) yield,
• M1/3 = [ N ρ(Π/6)] 1/3 . d. ----------------------------(10)
• The diameter d from equation (10) ,is substituted for 2r into equation
(8) to give...

22. • M1/3 = [ N ρ(Π/6)] 1/3 . 2r
• Mo
1/3 - M 1/3 = kt
• Mo = Original mass of drug particle
• k = [ N ρ (Π/6) ]1/3.2 k Cs/ρ = Mo
1/3 /d . 2k Cs / ρ cube
root dissolution rate constant
• t = time
• M = Nρ(π/6)d3
• N= No. of particles
• ρ = Density of particles
• d = Diameter of particles
Hixson – Crowell Cube root Law

23. Thank You