COMPACTION PROFILE & SOLUBILITY ENHANCEMENT TECHNIQUES NAVEEN BALAJI

1. COMPACTION PROFILES &
SOLUBILITY ENHANCEMENT TECHNIQUES
Presented by:
NAVEEN BALAJI
1st M.Pharm
Department of Pharmaceutics
Sree Siddaganga college of pharmacy
Tumakuru.
Under guidance of:
Dr.S.T.BHAGAVATHI,M.pharm,Ph.D,
Associate Professor
Department of Pharmaceutics
Sree Siddaganga college of pharmacy
Tumakuru.

2. CONTENTS
Compaction profiles.
Solubility Enhancement Techniques.
 Introduction
 Importance of Solubility.
 Techniques of Solubility Enhancement.

3. COMPACTION PROFILES
• The plot of radial pressure against axial pressure leads to
hysteresis curve called as Compaction profiles.
• Many attempts have been made to minimize the amount of
applied force transmitted radially to the die walls.
• All such investigations lead to characteristic hysteresis curves
called as Compaction profiles.
• Radial pressure is developed due to the attempt of material to
expand horizontally.

4. • When the elastic limit of the material is high,
elastic deformation may make the major
contribution & on removal of the applied
load, the extent of the elastic relaxation
depends on the value of the material’s modules
of elasticity (young’s modules).
• Lower the modules higher will be the elastic
relaxation. then there will be the danger of
structural failure.
• Higher the module value results in low
decompression, Hence lesser risk of structural
failure.

6. SOLUBILITY ENHANCEMENT TECHNIQUES

7. • SOLUBILITY :-
Solubility is defined as a interaction of two or more
substance to form a homogeneous molecular dispersion.
• SOLUBILIZATION:- is a process of breaking of
inter-ionic or intermolecular bonds in solute, the
separation of molecules of the solute to provide
space in the solvent for the solute.
INTRODUCTION

8. IMPORTANCE OF SOLUBILITY
• Therapeutic effectiveness of a drug depends upon the
bioavailability and ultimately upon the solubility of drug
molecule.
• It is important parameter to achieve desired concentration
of drug in systemic circulation for pharmacological
response.
• Any drug to be absorbed must be soluble or present in
the form of an aqueous solution at the site of absorption.

9. TECHNIQUES OF SOLUBILITY ENHANCEMENT
• 1) PHYSICAL MODIFICATION
• 2) CHEMICAL MODIFICATION
• 3) MISCELLANEOUS METHODS

10. 1) PHYSICAL MODIFICATIONs :-
• i) Particle size reduction
• ii) Modification of crystal habit
• iii)Drug dispersion in carriers
• iv) Complexation
• V)Solubilization by surfactants

11. PARTICAL SIZE REDUCTION
a) Micronization
b) Nano suspension
c) Sonocrystallisation
d) Supercritical fluid process

12. a) MICRONIZATION
• The process involves reducing the size of the solid
drug particles to 1 to 10 microns. This process is
also called as micro- milling.

13. • Micronization increases the dissolution
rate of drugs through increased surface
area.
• Micronization of drugs is done by milling
techniques using jet mill, rotor stator
colloid mills, etc.,.
• It is not suitable for drugs having a high
dose number because it does not change
the saturation solubility of the drug.

14. b) NANOSUSPENSION
• Nano suspension technology is used for efficient
delivery of hydrophobic drugs.
• Nano suspensions are sub-micron colloidal
dispersion of pure particles of the drug, which are
stabilized by surfactants.
• The particle size distribution of the solid particles in
nano suspensions is usually less than one micron
with an average particle size ranging between 200 to
600 nm.

15. c) SONOCRYSTALLISATION
• Particle size reduction on the basis of crystallisation by using
ultra sound is Sonocrystallisation. It utilizes ultra sound power
for inducing crystallisation.
• It not only enhances the nucleation rate but also an effective
means of size reduction & controlling size distribution of the
active pharmaceutical ingredients.
• Most applications use ultra sound in the range 20 kHz---5 MHz.

16. d) SUPERCRITICAL FLUID
PROCESS
• Supercritical fluids are dense non-condensable fluid whose
temperature & pressure are greater than its critical temperature
(Tc) and critical pressure (Tp) allowing it to assume the
properties of both a liquid and a gas.
• Through manipulation of the pressure of SCFs, the favourable
characteristics of gases-high diffusivity, low viscosity & low
surface tension may be imparted upon the liquids to precisely
control the solubilisation of drug with a supercritical fluid.
• Once the drug particles are solubilised within SCFs, they may
be recrystallized at greatly reduced particle sizes.
• SCF process allows micronisation of drug particles within
narrow range of particle size, often to sub-micron levels.

17. ii) MODIFICATION OF CRYSTAL
HABIT

18. • Metastable forms are associated with higher energy
and thus higher solubility. Similarly the amorphous
form of drug is always more suited than crystalline
form due to higher energy associated & increased
surface area.
• The anhydrous form of drug has greater solubility
than the hydrates. This is because the hydrates are
already in interaction with water & therefore have less
energy for crystal breakup in comparison to the
anhydrates.

19. • Thus, the order for dissolution of
different solid forms of drug is
• Amorphous > metastable
polymorph > stable polymorph
• Melting followed by a rapid cooling or
recrystallization from different solvents can
produce metastable forms of a drug.

20. iii) DRUG DISPERSION IN
CARRIERS
The term “solid dispersion” refers to the dispersion of
one or more active ingredients in an inert carrier in a solid
state, frequently prepared by the
i) Hot melt method
ii) Solvent evaporation method
iii) Hot melt extrusion method

21. a) HOT MELT METHOD :-
Drug + Vehicle
heated
Melted
Freezing quickly
Made into Dosage form
 A molecular dispersion can be achieved or not, it depends on the degree of
supersaturation and rate of cooling used in the process.
 Imp. Requisites :1) Miscibility of drug & carrier in the molten form. 2) Thermostability
of drug and carrier
 It is Not suitable for the drug & carrier which are unstable at higher temperature.

22. b) SOLVENT EVAPOURATION METHOD :-
Drug + Vehicle (both soluble in solvent)
Organic solvent
Evaporate the solvent
Coprecipitates
Dosage form
• The solvent evaporation can be done by spray drying or freeze drying.
• Temperature used for solvent evaporation mostly lies in the range between
23°-65°C.
• Suitable for the drugs with volatility and poor stability.

23. c) Hot-melt Extrusion:-
• Hot melt extrusion of miscible components
results in amorphous solid solution
formation, whereas extrusion of an
immiscible component leads to amorphous
drug dispersed in crystalline excipient. The
process has been useful in the preparation
of solid dispersions in a single step.

25. iv) Complexation :-
 The beta and gamma cyclodextrin having ability to
form molecular inclusion complexes with
hydrophobic drug having poor aqueous solubility.
 Cyclodextrin are versatile in having hydrophobic
cavity & suitable enough to accommodate the
lipophilic relatively hydrophobic drugs results in
improved aqueous solubility.
e.g: Barbiturates, Benzodiazepines.

26.  Surfactant reduces the interfacial tension.
 Enhance solubility by promoting wetting and
penetration of dissolution fluid into the solid
drug particles.
e.g: Spironolactone(steroids)--- increased
solubility by using surfactant(non ionic
polysorbates).
●
v) Solubilization By Surfactants :-

27. 2) CHEMICAL
MODIFICATIONS :-
i) Change in pH
ii) Use of buffer
iii) Derivatization

28. i) Change in pH :-
• For organic solutes that are ionizable, changing
the pH of the system is the simplest and most
effective means of increasing aqueous solubility .
Lower pH
Higher pH
More Soluble
Drug
Insoluble ppt
Ionized form
Unionized Form
Ionized form
More Soluble
Drug
Insoluble ppt
Lower pH
Higher pH
For Weakly Acidic Drugs
For Weakly Basic Drugs

29. ii) Use of buffer:
• Buffer maintains the pH of the
solution overtime and it reduces or
eliminate the potential for
precipitation upon dilution. On
dilution pH alteration occurs that
decrease solubility .

30. iii) Derivatization :-
It is a technique used in chemistry which
transforms a chemical compound into a product
of similar chemical structure, called derivative.
Derivatives have different solubility as that of
adduct. It is used for quantification of adduct
formation of esters and amides via acyl
chlorides

31. 3) MISCELLANEOUS METHODS :-
i) Co-solvency
ii) Solubilizing agents
iii) Porous Micro particle technology

32. i) Co-solvency :
• It is well-known that the addition of an organic co-solvent
to water can dramatically change the solubility of drugs.
• Weak electrolytes and nonpolar molecules have poor water
solubility and it can be improved by altering polarity of the
solvent.
• Co-solvent system works by reducing the interfacial tension
between the aqueous solution and hydrophobic solute.
• Aqueous solvent - Ethanol, sorbitol, glycerine, propylene
glycol. Non aqueous solvent - glycofurol, dimethyl acetamide.

33. ii) Solubilizing agents:
• The solubility of poorly soluble drug can also
be improved by various solubilizing materials.
PEG 400 is improving the solubility of
hydrochlorthiazide85.
• Modified gum karaya (MGK), a recently
developed excipient was evaluated as carrier
for dissolution enhancement of poorly soluble
drug, nimodipine .

34. iii) Porous microparticle technology:
• The poorly water soluble drug is embedded in
a microparticle having a porous, water
soluble, sponge like matrix, dissolves wetting
the drug and leaving a suspension of rapidly
dissolving drug particles. These drug particles
provide large surface area for increased
dissolution rate .

35. REFERENCES
 www.google.com
 Text book of biopharmaceutics and
pharmacokinetics by brahmankar.
 International journal of pharma professional’s
research review article solubility enhancement
techniques with special emphasis o n hydrotrophy
- volume 1, issue 1, July 2010.
 Journal of global pharma technology techniques
to enhance solubility of poorly soluble drugs