The document discusses dissolution testing of pharmaceutical solid dosage forms. It defines dissolution as the amount of drug substance that goes into solution per unit time under standardized conditions. Dissolution testing is important for quality control to ensure uniform drug release and bioavailability. The key mechanisms of dissolution are the diffusion layer model, Danckwert's model, and the interfacial barrier model. Factors that influence dissolution include apparatus parameters, drug properties, and dosage form composition. Common apparatus are the basket, paddle, and flow-through cell methods. Acceptance criteria and methods to enhance dissolution through nanonization or changes to formulation are also covered.

1. WELCOME
“Dissolution of Pharmaceutical Solid
Dosage Form”

2. Definition :
“the amount of drug substance that goes into solution per unit time under
standardized conditions of liquid/solid interface, temperature, solvent
composition .”

3. Importance
1. To show that the release of drug from the tablet is close to 100%.
2. To show that the rate of drug release is uniform batch to batch.
3. And to show that release is equivalent to those batches proven to
be bioavailable and clinically effective.
Applications
1. Important tool during development of dosage form.
2. Quality Assurance.
3. Product Stability.
4. Comparability Assessment.

4. Mechanism of Dissolution
1. Diffusion layer model
2. Danckwert’s model
3. Interfacial barrier model

5. 1.Diffusion Layer Model(film theory):
Formation of a thin film at the interface, called as stagnant
layer.
2 steps are involved:
A) Interaction of solvent with drug surface to forma
saturated drug layer , called stagnant layer.
B) Diffusion of drug molecules from stagnant layer into
bulk of the system

6. Noyes-Whitney’s equation:
Where,
D = diffusion coefficient of the drug
A = surface area of the dissolving solid
Kw/o = water/oil partition coefficient of the drug.
V = volume of dissolution medium
h = thickness of the stagnant layer
(Cs – Cb)= concentration gradient for diffusion of drug.

7. 2. Danckwert’s Model (Penetration or Surface Renewal
Theory)
This model suggest that turbulence in dissolution
medium exists at the solid/liquid interface. As a result, agitated fluid consisting
of macroscopic mass of eddies or packets reach the interface in random
fashion due to eddy currents, absorb the solute by diffusion and carry it to
bulk of the solution.
Such solute containing packets are continously replaced with new packets of
fresh solvent due to which drug conc. At S/L interface never reaches Cs and
has lower limiting value of Ci.

8. m = mass of solid dissolved
γ = rate of surface renewal (or the interfacial tension)

9. 3. Interfacial Barrier Model:
• Drug dissolution is a function of solubility rather than diffusion.
• Intermediate concentration exist at the interface as a result of
solvation.
• Dissolution rate per unit area, G is given by,
G= Ki(Cs-Cb)
where Ki = effective interfacial transport constant.

10. Dissolution Apparatus:
According to B.P. apparatus used are:
1. Apparatus I – BASKET APPARATUS
2. Apparatus II – PADDLE APPARATUS
3. Apparatus III – FLOW THROUGH CELL APPARATUS
According to USP 30 dissolution apparatus used are
1 . BASKET
2 . PADDLE
3 . RECIPROCATING CYLINDER
5 . PADDLE OVER DISK
6 . CYLINDER – (N/A )
7 . RECIPROCATING HOLDER

11. Apparatus 1- Basket apparatus:
DESIGN:
Vessel: -Made of borosilicate glass.
-Semi hemispherical bottom
-Capacity 1000ml
Shaft :
-Stainless steel 316
-Rotates smoothly without significance
wobble(100 rpm)
-Speed regulator
Water bath:
-Maintained at 37±0.5ºC.

12. USE:
Tablets, capsules, delayed release suppositories, floating
dosage forms.
Advantages
-Full pH change during the test
Can be easily automated which is important for routine
investigations.
Disadvantages
-Basket screen is clogged with gummy particles.
-Hydrodynamic „dead zone“ under the basket
-Degassing is particularly important
-Mesh gets corroded by HCl solution.

13. Apparatus 2- Paddle apparatus:
DESIGN:
Vessel:
-Same as basket apparatus
Shaft:
-The blade passes through the shaft
so that the bottom of the blade fuses with
bottom of the shaft.
Stirring elements:
-Stainless steel 316
Water-bath:
-Maintains at 37±0.5°C

14. Advantages:
• Easy to use
• pH change possible
• Can be easily adapted to apparatus
Disadvantages
• Floating dosage forms require sinker
• Positioning of tablet

15. Apparatus 3- Reciprocating cylinder:
Advantages:
1. Easy to change the pH-profiles
2. Hydrodynamics can be directly
influenced by varying the dip rate.
Disadvantages:
1. small volume (max. 250 ml)
• a set of cylindrical,
• flat- bottomed glass vessels;
• a set of glass reciprocating cylindrical;
• stainless steel fitting;
• screen;
• a motor and drive.
Standard volume: 200-250 ml/station

16. DISSOLUTION ACCEPTAN CECRITRIA
Q –Value:
Define as a percentage of drug content dissolved in a given time
period
Level Samples tested Acceptance criteria
S1 6 Each value is not less than Q + 5%
S2 6 Average value of the 12 dosage units (S1 +
S2 ) is equal to or greater than Q and no
unit is less than Q-15%
S3 12 Average value of 24 dosage units (S1 + S2
+ S3 ) is equal to or greater than Q; not
more than 2 units are less than Q - 15%; no
unit is less than Q - 25%.

17. Enhancement of dissolution rate of
tablet:
1. Micronization
2. Nanonization
A. Nanosuspensions
B. Nano crystals
C. Nano emulsion:
1. Micronization
Particle size reduction leads to increase in the effective surface
area resulting in enhancement of solubility and dissolution velocity
of the drug.
Micronization technique is used to improve dissolution rates of
drugs into the biological environment, in order to improve the oral
bioavailability

18. 2. Nanonization :
Various nanonization strategies have emerged to increase the
dissolution rates and bioavailability of numerous drugs that are
poorly soluble in water. Nanonization broadly refers to the study
and use of materials and structures at the Nano scale level of
approximately 100 nm or less.
A. Nanosuspensions:
Nanosuspensions are sub-micron colloidal dispersion of
pure particles of drug, which are stabilized by surfactants.
Nanosuspensions technology solved the problem of drugs
which are poorly aqueous soluble and less bioavailability

19. B. Nano crystals:
The term drug Nano crystals imply a crystalline state of the discrete
particles, but depending on the production method they can also be
partially or completely amorphous. Drug Nano crystals can be produced
by bottom up technologies (precipitation methods) or alternatively by
top down technologies (size reduction methods).
C. Nano emulsion:
Nano emulsions are a nonequilibrium, heterogeneous system
consisting of two immiscible liquids in which one liquid is dispersed as
droplets in another liquid.

20. Factors that Influence Dissolution Testing:
Factors affecting Drug Dissolution :-
1. Factors related to apparatus and test parameters
2. Factors relating to the physicochemical properties of drug.
3. Factors relating to the dosage forms
1. FACTORS RELATED TO APPARATUS AND TEST
PARAMETERS
1.Temperature
2. Agitation

21. 1. Agitation
-Rate of dissolution depends on type of agitation used, the degree of
laminar and turbulent flow in system, the shape and design of stirrer. -
Speed of agitation should be such that it prevent turbulence and sustain a
reproducible laminar flow, which is essential for obtaining reliable results. -
So, agitation should be maintained at a relatively low rate
2. Temperature
-Should be maintained at 37 ± 0.5 º C 4

22. 2. Factors relating to the physicochemical
properties of drug-
1. Solubility-
• Solubility plays important role in controlling dissolution from dosage form.
• From Noyes-Whitney equation it shows that aqueous solubility of drug
which determines its dissolution rate
ii. Particle size and effective surface area of the drug –
• Particle size and surface area are inversely related to each other.
Two types of surface area –
Absolute surface area which is the total surface area of any particle.
Effective surface area which is the area of solid surface exposed to the
dissolution medium

23. • Effective surface area is directly related to the dissolution rate.
• Greater the effective surface area, more intimate the contact between the
solid surface and the aqueous solvent and faster the dissolution.
iii. Polymorphism and amorphism –
• When a substance exists in more than one crystalline form, the different
forms are designated as polymorphs and the phenomenon as
Polymorphism.
• Amorphous form of drug which has no internal crystal structure
represents higher energy state and greater aqueous solubility than
crystalline forms.

24. IV. Salt form of the drug-
• Dissolution rate of weak acids and weak bases can be enhance by
converting them into their salt form.
• With weakly acidic drugs, a strong base salt is prepared like sodium
and potassium salts of barbiturates and sulfonamides.
• With weakly basic drugs, a strong acid salt is prepared like the
hydrochloride or sulfate salts of alkaloidal drugs

25. 2. Factors relating to the dosage forms –
Pharmaceutical excipients –
1. Binder and granulating agents:
2. Disintegrants
3. Lubricants
4. Coatings
5. Complexing agents
1. Binders and granulating agents:
- In general, the hydrophilic ( aqueous) binders show better
dissolution profile with poorly wettable drugs like phenacetin by
imparting hydrophilic properties to the granule surface.
- Large amounts of such binders increase hardness and decrease
disintegration / dissolution rates of tablets.

26. 2. Disintegrants
- Disintegrating agent added before & after the granulation affects
the dissolution rate.
- Microcrystalline cellulose is a very good disintegrating agent but at
high compression force, it may retard drug dissolution.
- Starch is not only an excellent diluent but also superior disintegrant
due to its hydrophilicity and swelling property.
3. Lubricants:
- The nature, quantity, and quality of lubricants added can
affect the dissolution rate.
- Lubricants are hydrophobic in nature (several metallic
stearate & waxes) which inhibit wettability, penetration of water
into tablet so decrease in disintegration and dissolution

27. 4. Coatings
-In general, the deleterious effect of various coatings on drug dissolution from
a tablet dosage form is in the following order: Enteric coat > Sugar coat >
Non- enteric film coat.
5. Buffers
- Buffers are sometimes useful in creating the right atmosphere for drug
dissolution, e.g. buffered aspirin tablets.
6. Complexing agents
- A complexed drug may have altered stability, solubility, molecular size,
partition coefficient and diffusion coefficient.
- E.g. Enhanced dissolution through formation of a soluble complex of
ergotamine tartarate-caffeine complex and hydroquinone-digoxin complex

28. A. Method of granulation
- Wet granulation has been shown to improve the dissolution rate of
poorly soluble drugs by imparting hydrophilic properties to the surface of
granules.
3. Factors relating to the dosage forms
B. Compression force
- The compression process influence density, porosity, hardness, disintegration
time & dissolution of tablet.

29. Conclusion :
By studying various factors influencing the rate of dissolution, we can
optimize the different properties of the formulation. By conducting
dissolution studies we can know the batch to batch reproducibility.
We can estimate the solubility profiles of the drug.
The best available tool today which can at least quantitatively assure
about the biological availability of drug from its formulation is its invitro
dissolution.

30. “Prevention Is Better
Than Cure”
THANKS