In this slide contains impotence of solubility, solubilization and Effect of Compression on Solubility. Presented by: T. MOUSAMI BHAVASAR(Department of pharmaceutics). RIPER, anantapur

1. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 1
Tablet solubility and Effect of
compression on solubility
A Seminar as a part of curricular requirement
for I year M. Pharm I semester
Presentedby
T. Mousami Bhavasar
(Reg. No. 20L81S0302)
Under the guidance
Dr. CH Pavan Kumar
M. Pharm, Ph.D
Associate Professor, Head
Dept. of Pharmaceutics

2. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 2
• Introduction
• Importance of solubility
• Solubilization
• Solubility enhancement techniques
• Effect of compression on solubility
• References
Contents

3. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 3
Introduction
Solubility:
1. Qualitative terms:
Solubility is defines as, “the spontaneous interactions of two
or more substancesto form a homogeneous molecular dispersion”.
2. Quantitative terms:
Solubility is defined as, “the concentration of a solute in a
saturated solvent at a constanttemperature”.

4. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 4
• Low aqueous solubility is the major problem encounteredwith
formulation development of new chemical entities as well as for
generic development.
• More than 40% new chemical entities developed in pharmaceutical
industry are practically insoluble in water. Solubility is a major
challenge for formulation scientist.
• Any drug to be absorbed must be present in the form of solution at
the site of absorption.

5. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 5

6. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 6
Class Solubility Permeability
I High High
II Low High
III High Low
IV Low Low
The Biopharmaceutical Classification System (BCS)

7. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 7
• A drug is considered to be highly soluble when the highest dose
strength is dissolved in 250ml or less of aqueous medium over a pH
range of 1-8.
• A drug is considered to be highly permeable when the extent of drug
absorption may expected to be more than 90% of administered
dose.
Q: A drug whose solubility is 1gm/lit in water when given orally at a
dose of 500mg is absorbed upto 95% of administered dose. That
drug belongs to which class according to BCS?

8. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 8
Definition Parts of solvent requiredfor 1
part of solute
Very soluble <1
Freely soluble 1-10
Soluble 10-30
Sparingly soluble 30-100
Slightly soluble 100-1000
Very slightly soluble 1000-10000
Insoluble >10000
The Pharmacopoeia lists solubility in terms of number of millilitres
of solvent required to dissolve 1g of solute. The IP provides general
terms to describe a given range. The description terms as given as:

9. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 9
• Therapeutic effectiveness of a drug depends upon the bioavailability
and ultimately upon the solubility of drug molecule.
• Solubility is one of the important parameter to achieve desired
concentration of drug in systemic circulation for pharmacological
response to be shown.
• Poorly water soluble drugs often requires high doses in order to
reach therapeutic plasma concentrations after oral administration.
Importance of Solubility

10. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 10
The process of solubilization involves the breaking of inter ionic or
intermolecular bonds in the solute, the separation of the molecules
of the solvent to provide space in the solvent for solute, interaction
between the solvent and the solute molecule or ion.
Solubilization

11. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 11
• There are variety of new drugs & derivatives are available. But less
than 40% of lipophilic drugs fails to reach market due to poor
bioavailability, even though these drugs might exhibit pharmaco-
dynamic activities.
• The lipophilic drug that reaches market requires a high dose to attain
proper pharmacological action.
• The basic aim of further formulation & development is to make that
drug available at proper site of action within optimum dose.
Need for solubility enhancement

12. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 12
Solubility enhancement techniques
1. Physical modification
A. Particle size reduction
a. Micronization
b. Nanosuspension
c. Sonocrystallization
d. Super critical fluid process
B. Modification of the crystal habit
a. Polymorphs
b. Pseudopolymorphs

13. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 13
C. Drug dispersion in carriers
a. Eutectic mixtures
b. Solid dispersion
c. Solid solutions
D. Complexation
Use of complexing agents
E. Solubilization by surfactants
Microemulsions

14. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 14
2. Chemical Modifications
A. Change in the pH
B. Use of buffer
C. Derivatization
3. Other Modifications
A. Co-crystallisation
B. Co-solvency
C. Hydrotrophy
D. Solubilizing agents

15. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721
E. Selective adsorption on insoluble carrier
F. Solvent deposition
G. Using soluble prodrug
H. Functional polymer technology
I. Precipitation porous
J. Microparticle technology
K. Nanotechnologyapproaches

16. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 16
Effect of compressionon tablet
solubility

17. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 17
Various factors will affect tablet solubility like hardness, specific
surface area, porosity, disintegration, dissolution.
i. Hardness:

18. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 18
• Compression forces increases, the hardness of the tablet increases
due to high compact arrangement of the granules in the tablet, so
the tablet requires more time and effort to get dissoluted in the
dissolution medium.
• There is a linear relationship between tablet hardness and logarithm
of applied pressure except at high pressure.
• As shown in figure, for lactose-aspirin tablets, compressed mixture
have hardness values between those of tablets composed of the
individual ingredients.
• Thus, as hardness increases, disintegration time will also increases,
which further leads to the decrease in solubility.

19. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 19
2. Specific surface area
• Specific surface is the measure of 1 g of material.
• The influence of applied pressure on the specific surface area of a
tablet is shown in this figure.

20. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 20
• As the lactose granules, which are granulated by adding 10% starch
paste are compressed, the specific surface is increased to maximal
value, indicating the formation of new surfaces due to fragmentation
of the granules.
• Further increases in applied pressure produce a progressive
decrease in specific surface area as the particles bond.
• A similar relation is shown for aspirin containing 10% starch.
• When an equal weight of aspirin and lactose is blended with 10%
starch and then compressed ,the specific surface is between that of
aspirin and lactose tablets individually.
• Thus, as compression forces increases, surface area of the tablet that
is exposed to the dissolution medium will be reduced, so the
dissolution rate will be minimized which further leads to decrease in
solubility.

21. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 21
3. Porosity
• When a particles of a large size is subjected to light compression, the
tablet will be high porous, which leads to low tablet strength.
• Reduction in porosity is due to granule fragmentation giving smaller
particles which may be more closely packed and plastic deformation
which allows the granules to flow into void spaces.
• If porosity decreases, it results in a decreased water ingression and
this will result in a slower rate of dissolution.
• As rate of dissolution decreases, the solubility is also decreases for
the drug.

22. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 22

23. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 23
4. Disintegration:
• Usually, as the applied pressure used to prepare a tablet is increased,
the disintegration time is longer.
• There is an exponential relationship between the disintegration time
and applied pressure , as shown in this figure.

24. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 24
• For tablets compressed at low pressure, there is a large void, and the
contact of starch grains in the interparticular space is discontinuous.
• Thus, there is a lag time before the starch grains, which are swelling
due to imbibitions of water, contact and exert a force on the
surrounding tablet structure.
• For tablets compressed at a certain applied pressure, the contact of
starch grain is continuous with the tablet structure, and swelling of
starch grains immediately exerts pressure, causing the most rapid
disintegration.

25. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 25
• For tablets compressedwith pressure greater than that producing
the minimum disintegration time, more time is required for
penetration of water into the tablet due to decrease in porosity,
which resulting increase in disintegration time.
• As the disintegration time increase, the dissolution rate also
decreases, thus it will affect the drug solubility.

26. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 26
5. Dissolution
• The effect of applied pressure on dissolution rate may be considered
from the viewpoint of non-disintegrating tablets and disintegrating
tablets.
• The effect of applied pressure on dissolution of disintegrating tablets
is difficult to predict.
• If fragmentation of granules occurs during compression, the
dissolution is faster as the applied pressure is increased, because of
increase in specific surface area.
• If the bonding of particle predominantly occurs during the
compression,then it decreases the dissolution.

27. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 27
• Tablets prepared at high compression forces are expected to exhibit
smaller specific surface area, smaller porosity, higher tablet density
and hardness which further leads to increase in disintegration time
than tablets prepared at low compressionforces.
• In many cases, the combined effect of these factors will reflect on
tablet dissolution.
• In such conditions, the rate of dissolution will decreases with the
increase in applied compression forces.

28. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 28

29. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 29
• The curve obtained by plotting compressionforce versus rate of
dissolution can take one of the 4 possible shapes.

30. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 30
• First condition, higher compressionforce increases the density of
tablets, decreases the porosity and hence the penetrability of
solvent into the tablet retards wettability. In many cases, tighter
bonding between the particles so decreases dissolution rate of
tablet.
• Second condition, higher compressionforce causes deformation,
crushing or fracture of drug particles into smaller ones or convert
spherical granules into disc shaped particles with a large increase in
the effective surface area, so increase in dissolution rate.
• Third condition, the dissolution rate is faster to a maximum as the
force is increased, and further increase in force slow downs
dissolution.
• Fourth condition, the dissolution is slowed to a minimum as pressure
is increased and further increase in pressure speeds dissolution.

31. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 31
• Roberts RJ, Rowe RC. Brittle/ductile behaviour in Pharmaceutical
materials used in tabletting. Int J Pharm. 1987; 36: 205-209.
• Huttenrauch R, Fricke S, Zielke P. Mechanical activation of
pharmaceutical systems. Pharm Res. 1985; 2: 302-306.
• Sarsavatkumar Patel, Aditya Mohan Kaushal & Arvind Kumar Bansal.
Department of Pharmaceutical Technology(Formulation), National
Institute of Pharmaceutical of Pharmaceutical Education and
Research(NIPER), S.A.S. Nagar, India.
References

32. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.PalliCross, Chiyyedu, Anantapuramu, A. P- 515721 32