This document discusses drug dissolution and release from solid oral dosage forms. It provides 3 key points: 1) Dissolution is the process by which a solid drug forms a solution when it comes into contact with fluid in the body. The drug must dissolve before it can be absorbed and produce its pharmacological effects. 2) Several factors can impact the rate of drug dissolution including the drug's solubility, particle size, polymorphism, as well as formulation factors like excipients and manufacturing methods. 3) Common mathematical models like the Noyes-Whitney equation and Hixson-Crowell cube root law are used to describe and quantify drug dissolution kinetics based on assumptions like diffusion layer thickness and geometric

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

2. Drug Release
• Drug release is processes by which a drug
leaves a drug product and it is subjected
to ADME to be available for
pharmacological action

3. Drug release
• Immediate release
• Modified release
– Delayed release (more than immediate)
– Extended release (long time)
• Controlled release
– Extended -pulsatile

4. Drug release

5. Dissolution
• Dissolution refer to the processes by
which a solid phase (tablet or powder)
goes into solution (water)
• Solubility: Maximum amount of solute that
a pure solvent can hold.

6. Dissolutionn from solid
dosageform (Tablet)

7. 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 drug-dissolution.

8. Dissolution Mechanism

9. 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

10. 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

11. 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

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

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

14. 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

15. Calibration curve

16. Dissolution graph

18. 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.

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

20. Intrinsic Dissolution Rate
• Mathematically intrinsic dissolution rate can be
expressed by Noyes Whitney equation
• dM/dt = DS(Cs-C) /h
• 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 solid (solute)
• C= concentration of solute at time t
• dM/dt = KS (Cs-C)
• At sink condition dM/dt = KS Cs

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

22. Hixson – Crowell Cube root Law
Dosage-form's dimensions reduces 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

24. 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 the Noyes-
Whitney equation is
• -dM = k.S.Cs.dt ---------------------------(4)... (k=D/h), (dM= ρdV)

25. • 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...

26. • M1/3 = [ N ρ(Π/6)] 1/3 . 2r
• Mo
1/3 - M 1/3 = kt
• Mo = Original mass of drug particles
• 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 = Mass of N no. of particles Nρ(π/6)d3
• N= No. of particles
• ρ = Density of particles
• d = Diameter of particles
Hixson – Crowell Cube root Law

27. Thank You