brief introduction of drug dissolution

2. CONTENTS…
 Definitions
 Drug dissolution process
 Theories of dissolution
 Factors affecting drug dissolution
and dissolution rate
 Official methods of dissolution
 Conclusion
 References

3. DEFINITION:
Dissolution is a process in which solid
substance solubilises in a given solvent i.e.,
mass transfer from the solid surface to the
liquid phase.
Dissolution rate is defined as the amount
of solid substance that undergoes into
solution per unit time under standard
conditions of temperature, pH and solvent
composition and constant surface area.

4.  The effectiveness of a tablet in releasing the drug for
absorption depends upon four steps
step:1 Breaking of tablets into granules (disintegration)
Step:2 Some times, times the granules further break into small
fine particles (deaggregation)
Step:3 The release of drug into solution (dissolution)
Step:4 Absorption
DRUG DISSOLUTION
PROCESS:

6. WHY DISSOLUTION STUDIES??
1. To show release of drug from the
tablet is close to 100%
2. To show that rate of drug release is
uniform batch to batch.
3. To show that release is equivalent to
those batches proven to be
bioavailable and clinically effective.

7. THEORIES OF DRUG
DISSOLUTION:
1. Diffusion layer model/Film
theory
2. Danckwert’s model/Surface
renewal theory
3. Interfacial barrier theory/
Limited solvation theory

8. 1. DIFFUSION LAYER MODEL / FILM THEORY:
The process of dissolution of solid particles in a
liquid involves two steps:
1. Solution of the solid to form a thin layer or film at
the solid / liquid interface called the Stagnant
film or diffusion layer which is saturated with
the drug.
2. Diffusion of the soluble solute from the stagnant
layer to the bulk of the solution.

10.  The rate of dissolution is given by Noyes and Whitney
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.

11. This above equation is based on the Fick’s second law of
diffusion.
Nernst and Brunner incorporated Fick’s first law of diffusion
and modified the Noyes-Whitney equation:
dC/dt = DAKw/o (Cs-Cb)
Vh
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

12.  This is first order dissolution rate process, for
which the driving force is the concentration gradient
 This is true for in-vitro dissolution which is
characterized by non-sink conditions.
 The in-vivo dissolution is rapid as sink conditions
are maintained by absorption of drug in systemic
circulation i.e; Cb=0 and rate of dissolution is
maximum.
 Under sink conditions, if volume and surface of the
solid are kept constant then,
dc/dt=k
 This represents that dissolution rate is constant
under sink conditions and follows zero order
kinetics.

13. DISSOLUTION RATE UNDER SINK AND
NON-SINK CONDITIONS:

14. 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 involve constant use of surface
area discs are employed to determine the rate of dissolution.
 To account for the particle size decrease and change in surface
area accompanying dissolution, Hixson and Crowell’s cubic
root law of dissolution is used:
Wo
1/3
– W
1/3
= K.t
where,
W = mass of drug remaining to be dissolved at time t
K = dissolution rate constant
Wo = original mass of the drug

15. 2. DANCKWERT’S MODEL:
 Also called as Penetration or surface renewal theory.
 Danckwert’s takes into account that eddies or
packets that are present in the agitated fluid which
reach the solid-liquid interface, absorb the solute by
diffusion and carry it out into the bulk of the solution
 The solute containing packets are continuously
replaced by new ones and exposes to new solid
surface each time, thus the theory is called as
Surface renewal theory.

16. The Danckwet’s model is expressed by the equation
m = mass of solid dissolved, and
γ = rate of surface renewal (or the
interfacial tension)

17. 3. INTERFACIAL BARRIER MODEL:
 Also called as Double barrier Or Limited
solvation theory
 According to this theory , an intermediate
concentration can exist at the interface as a
result of solvation mechanism and is a
function of solubility rather than diffusion.
 Such a concept is given by the equation:

18. FACTORS AFFECTING DRUG
DISSOLUTION AND DISSOLUTION RATE:
1. Physicochemical properties of
the drug
2. Dosage form Factors
3. Patient related factors

19. 1. PHYSICOCHEMICAL FACTORS:
1. Particle size and effective surface area:
Particle size and surface area of a solid are inversely related to
each other. Smaller the drug particle greater the surface
area.
Two types of surface area :
A. Absolute surface area which is total area of solid
surface of any particle.
B. Effective surface area which is the area of solid
surface to the dissolution medium.

20.  According to Noyes-whitney’s equation larger the surface
area higher the dissolution rate.
 Since, the surface area increases with decreasing the particle
size, which can be accomplished by micronisation, will result
in higher dissolution rates.
 Greater the surface area more intimate the contact b/w the
solid surface and the aqueous solvent and faster the
dissolution.
EXAMPLES:
 Griseofulvin- 250mg
 Spiranolactoine- 20mg

21. 2. POLYMORPHISM AND AMORPHISM
When a substance exist in more than one crystalline form, the
different forms are designated as Polymorphs and the
phenomenon as Polymorphism
Polymorphs are two types:
A. Enantiotropic polymer is the one which can be
reversibly changed into another form by altering the
temperature or pressure. Ex: Sulphur.
B. Monotropic polymer is the one which is unstable
at all temperatures and pressures. Ex: Glyceryl stearates.
Depending on the relative stability polymeric forms
will be more stable than the others.

22.  Stable polymorphs represents the low energy state, has high
melting point and least aqueous solubility.
 Metastable forms represent high energy state , has lower
melting point and high aqueous solubility thereby, better
Bioavailability.
 Due to higher energy state, has thermodynamic tendency to
convert to stable form.
Examples:
 Chloramphenicol palmitate A, B and C, the B form is best
available and the A form is inactive biologically.
 Riboflavin form III is 20 times more water soluble than form I

23. Some drugs exists in Amorphous form i.e, having no
internal structure.
Such drugs represent higher energy state and can be
considered as supercooled liquids.
These have greater aqueous solubility than the crystalline
forms.
Examples:
 Amorphous form of novobiocin is 10 times more stable than
crystalline form.
 Chloramphenicol palmitate
 Cortisone acetate
Therefore;
Amorphous> Metastable> Stable

24. 3. SALT FORM OF THE DRUG
 Most drugs are either weak acids or weak bases
 To enhance the solubility and dissolution rate of such drugs
is to convert them into their salt forms.
 Generally weak acidic drugs, a strong base salt is prepared
such as sodium and potassium salts of barbiturates and
sulphonamides.
 In case of weakly basic drugs, a strong acid salt is prepared
like the hydrochloride or sulphate salts of several alkaloid
drugs.

25. 2. DOSAGE FORM FACTORS:
 A drug is rarely administered in its original form.
 Excipients are added to ensure acceptability,
physicochemical stability during the shelf-life, uniformity of
composition and dosage and optimum bioavailability.
1. Vehicle: is the major component of liquid orals and
parentrals.
 Aqueous : water, syrup etc;
 Non-aqueous: sorbitol, glycerol etc;
Bioavailability of the drug from vehicles depends to a
large extent on its miscibility with the biological
fiuids.

26. 2. Diluents(fillers): commonly added to tablets where the
drug is very potent and less dose so to produce necessary
bulk.
Organic diluents: Starch, lactose, micro crystalline cellulose.
Inorganic diluent: Dicalcium phosphate.
3. Binders and granulating agents: Materials to hold
powders to form granules or promote cohesive compacts for
directly compressable materials.
Examples: Starch, cellulose derivatives like gelatin, ethyl
cellulose, methyl cellulose, HPC; PVP, acacia.

27. OFFICIAL METHODS OF DISSOLUTION

28. ACCORDING TO INDIAN PHARMACOPEIA :
Two types of apparatus are present:
 Type I - Paddle apparatus
 TypeII - Basket apparatus.

29. ACCORDING TO USP:

37. CONCLUSION:
 By studying various factors influencing rate of dissolution,
we can optimize the different properties of the formulations.
 By conducting dissolution studies we can know the batch to
batch reproduciblity
 We can estimate the solubility profile of the drugs.
 The best available tool today which can atleast quantitatively
assure about the biological availability of the drug from its
formulation is its in-vitro dissolution.

38. REFERENCES:
 Brahmankar, D. M; Sunil B. jaiswal,
Biopharmaceutics and Pharmacokinetics – A
Treatise, 3rd edition, vallabh Prakashan, New Delhi.
Page No. 29-56
 C.V.S. Subhramanyam (2000), “ Text book of
physical pharmaceutics” Vallabh Prakashan, 2nd
Edition, Page No. 85-105
 United States Pharmacopoeia, Page No. 24
1942-1951.