1.

DEFINATION : • Dissolution rate may be defined as amount of drug substance that goes in the
solution per unit time under standard conditions of liquid/solid interface, temperature and solvent
composition. It can be consider as a specific type of certain hetrogenous reaction in which mass
transfer results as a net effect between escape and deposition of solute molecule at a solid surface. •
3INTRODUCTION
2. 4. The processes involved in dissolution of solid dosage forms: 4
3. 5. Initial mechanical lag Wetting of dosage form Penetration of dissolution medium Disintegration
Deaggregation Dissolution Occlusion of some particles 5      MECHAMISM OF
DISSOLUTION
4. 6. IDR should be independent of boundary layer thickness and volume of solvent. Thus IDR measures
the intrinsic properties of the drug only as a function of the dissolution medium, e.g. its pH, ionic
strength, counters ions etc. 6 Intrinsic dissolution rate (IDR), which is the rate of mass transfer per
area of dissolving surface and typically has the units of mg cm-2 min-1. Intrinsic dissolution 2 rate
5. 7. Cb - concentration of the substance in the bulk of the solvent, kg/m3 7 Cs - concentration of the
substance on the surface, kg/m3  d - Thickness of the boundary layer of the solvent at the surface of
the dissolving substance, m  D - Diffusion coefficient, m2/s coefficient  A - Surface area of the
interface between the dissolving substance and the solvent,m2  t - Time, seconds  m - Amount of
dissolved material, kg Rate of dissolution Where:
6. 8. 3 Importance: 1. Results from in-vitro dissolution rate experiment can be used to explain the
observed difference in invivo availability 2. Dissolution testing provides the means to evaluate critical
parameters such as adequate bioavailability and provides information necessary to formulator in
development of more efficacious and therapeutically optimal dosage forms. 3. Most sensitive and
reliable predictors of in-vivo availability. 8Importance and Application
7. 9. 4. Dissolution analysis of pharmaceutical dosage forms has emerged as single most important test
that will ensure quality of product. 5. It can ensure bioavailability of product between batches that meet
dissolution criteria. 6. Ensure batch-to-batch quality equivalence both in-vitro and in-vivo, but also to
screen formulations during product development to arrive at optimally effective products. 7.
Physicochemical properties of model can be understood needed to mimic in-vivo environment. 9
8. 10. 8. Such models can be used to screen potential drug and their associated formulations for
dissolution and absorption characteristics. 9. Serve as quality control procedures, once the form of
drug and its formulation have been finalized. 10
9. 11. Application:2 11
10. 12. PRODUCT DEVELOPMENT Important tool during development of dosage form. Aids in guiding
the selection of prototype formulations and for determining optimum levels of ingredients to achieve
drug release profiles, particularly for extended release formulations. Also guides in selection of a
“market-image” product to be used in pivotal in-vivo bioavailability or bioequivalence studies. QUALITY
ASSURANCE D.T. performed on future production lots and is used to assess the lot-to-lot
performance characteristics of drug product and provide continued assurance of product
integrity/similarity. 12     
11. 13. 13 In-vitro dissolution also used to assess drug product quality with respect to stability and
shelflife. As product age, physicochemical changes to the dosage form may alter dissolution
characteristics of drug product over time. For some products, polymorph transformations to more
stable, and hence less soluble crystalline forms may result in reduced dissolution rates.  PRODUCT
STABILITY 
12. 14. COMPARABILITY ASSESSMENT Also useful for assessing the impact of pre- or post- approval
changes to drug product such as changes to formulation or manufacturing process. Thus, in-vitro
comparability assessment is critical to ensure continued performance equivalency and product
similarity. WAIVERS OF IN-VIVO BIOEQUIVALENCE REQUIREMENTS In-vitro dissolution testing or
drug release testing may be used for seeking waiver of required product to conduct in-vivo
bioavailability or bioequivalence studies. 14   
13. 15. Theories Of Dissolution 4 I. Diffusion layer model/Film Theory II. Danckwert’s model/Penetration or
surface renewal Theory III. Interfacial barrier model/Double barrier or Limited solvation theory 15
14. 16. It is a simplest model where dissolution of crystal, immersed in liquid takes place without involving
reactive or electrical forces. Consist of two consecutive steps: 1. Solution of the solid to 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). 2. 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. The model is depicted in following fig. 16I. Diffusion layer model/Film Theory
15. 17. 17
16. 18. The rate of dissolution is given by Noyes and dc Whitney: k (C - C ) dt s b Where, dc/dt=
dissolution rate of the drug K= dissolution rate constant Cs= concentration of drug in stagnant layer
Cb= concentration of drug in the bulk of the solution at time t 18
17. 19. Brunner   & Tolloczko incorporated surface area „A‟ in Noyes & Whitney equation. dc/dt = k1A
( Cs – Cb ) Afterwards Brunner, incorporated Fick‟s law of diffusion & expanded his given eq to include
diffusion coefficient „D‟, thickness of stagnant diffusion layer „h‟ & volume of dissolution medium „v‟.
19
18. 20. Modified Noyes & Where, D= diffusion coefficient of drug. A= surface area of dissolving solid.
Kw/o= water/oil partition coefficient of drug. V= volume of dissolution medium. h= thickness of stagnant
layer. (Cs – Cb )= conc. gradient for diffusion of drug. 20      Whitney equation dc/dt =DAKw/o
(Cs- Cb) /Vh
19. 21. This eq describes a first – order dissolution kinetics. It represents dissolution under non-sink
conditions. If volume is relatively large such that Cs  >>>Cb so, dc/dt =AKw/o Cs/Vh Cs & D are
constant for each specific chemical substance so dc/dt =k1 A /Vh (k1= Kw/o D Cs) V & A are kept
constant during dissolution so dc/dt =k 21
20. 22. Sink condition A Sink conditions describe a dissolution system that is sufficiently dilute so that the
dissolution process is not impeded by approach to saturation of the compound of interest. Sink
conditions affect the production of the sample but not the condition of the solution upon sampling. In
vivo condition, there is no conc. build up in the bulk of the solution and hence no retarding effect on the
dissolution rate of the drug i.e. Cs>>Cb and sink condition maintain. 22
21. 23. First order under non sink condition Time 23Dissolution rate under sink condition follow zero
order dissolution rate. Zero order dissolution Under sink condition Conc of disslove drug
22. 24. 24 In vitro sink condition is so maintain that Cb always less than 10% of Cs. For obtaining
IVIVC sink condition can be achieved by: 1) Bathing the dissolving solid in fresh solvent from time to
time. 2) Increasing the volume of dissolution fluid. 3) Removing the dissolved drug by partitioning it
from the aqueous phase of dissolution fluid into the organic phase placed either above or below the
dissolution fluid for e.g. hexane or chloroform. 4) Adding a water miscible solvent such as alcohol to
the dissolution fluid. 5) By adding selected adsorbents to remove the dissolution drug.
23. 25. HIXON-CROWELL CUBE ROOT RELATIONSHIP Major assumptions in Noyes-Whitney
relationship is that the S.A. (A) term remains constant throughout dissolution process. This is true for
some formulations, such as transdermal patches. However, size of drug particles from tablets,
capsules and suspensions will decrease as drug dissolves. This decrease in size of particles changes
the effective S.A. Thus, Hixon     & Crowell modified the eq to represent rate of appearance of
solute by weight in solution by multiplying both sides of volume term. W01/3– W1/3 = kt W0 = original
mass of drug W = mass of drug remaining to dissolve at time t K = dissolution rate constant 25
24. 26. 26   This theory assumes that solid-soln equilibrium is achieved at interface and mass
transport is slow step in dissoln process. The model could be visualized as a very thin film having a
conc. Ci which is less than saturation, as it is constantly being exposed to fresh surfaces of liquid
having a conc. much less than Ci. Acc. to model, the agitated fluid consist of mass of eddies or
packets that are continuously being exposed to new surfaces of solid and then carried back to bulk of
liquid. Diffusion occurs into each of these packets during short time in which the packet is in contact
with surface of solid. Since turbulence actually extends to surface, there is no laminar boundary layer
and so no stagnant film exists. Instead, surface continually being replaced with fresh liquid. 
DANCKWERT’S MODEL (PENETRATION OR SURFACE RENEWALTHEORY) 
25. 27. 27
26. 28. Interfacial barrier model (double barrier or limited salvation theory) Based on salvation
mechanism & solubility rather than diffusion. When considering the dissolution of the crystal will have
a different interfacial barrier given by following equation, G = ki (Cs – Cb) Where G = dissolution per
unit area Ki = effective interfacial transport constant In this theory, the diffusivity D may not be
independent of saturation conc. Cs . The interfacial barrier model can be extended to both diffusion
layer model and the Dankwert’s model. 28