Solubility improvemecnt techniqucs can be categorizeddiin

tophysical modification, chemical modifications of the

drug substance,and other tcchniques.
Physical Modifications
Particle size reduction like micronization and
nanosuspension, modification of the crystal habit like
polymorphs, amorphous form and cocrystallization, drug
dispersion in carriers like eutectic mixtures, solid
dispersions, solid solutions and cryogenic techniques.
Chemical Modifications
Change ofph,use ofbuffer, derivatization, complexation,
and salt formation.

Miscellaneous Methods
Supercritical fluid process, use of adjuvantlike surfactant,
solubilizers, cosolvency, hydrotrophy, and novel excipients.
Micronization
effective
Particle size reduction leads to increase in the
solubility
surface area resulting in enhancement of
and dissolution velocity ofthe drug.
dissolution
Micronization technique is used to improve
environment, in order
rates ofdrugs into the biological
improve the oral bioavailability. Particle size
to recrystallization of the
reduction methods include
using liquid antisolvents,
solute particles from solutions
with labor intensive techniques like crushing,
along spray-drying.
milling, grinding, freeze drying and
expansion of supercriticalsolutions (RESS)
The rapid micronization of
technique for the
isan alternative carbon dioxide to quickly
particles using supercritical
reduce the particle sizes of variousdrugs.
and naturally limitations; micronization of
Micronization has some a
poorly soluble drugs is by no means
sparingly or dissolution and absorption. A
guarantee of better small particle size leads to
hydrophobicpowderwith difficult todisperse.
aggregation, making it because
the dissolution medium
float on
The particles difficult to remove or wet these
It is of
ofentrapped air. effects, in fact, reduce the rate
particles. Allthese
dissolution.
 Sonocrystallization
Sonocrystallization is a novel particle engineering
technique to cnhancc solubility and dissolution of
hydrophobic drugs andto study its effect on crystal
propertics of drug.
Recrystallization of poorlysoluble materials using liquid
solvents and antisolvents has also been employed
successfully to reduce particle size by using ultrasound.
Sonocrystallization utilizes ultrasound power
characterized by a frequency range of 20-100 kHz
for inducing crystallization. Most applications use
ultrasound in the range 20 kHz-5 MHz. Melt
sonocrystallization (MSC) is promising technique of
sonocrystallization to obtain porous, amorphous
material with high stability.
Supercritical fluid method
Asupercritical fluid (SCF) can be defined as a
dense
noncondensable fluid is a novel nanosizing and
solubilisation technology. ASCF process allows the
micronization of drug particles within sub micron levels.
Supercritical fluids are fluids whose temperature and
pressure are greater than critical
and critical pressure (Tp). Attemperature (Tc)
temperature, SCFs are highly compressible,near-critical
moderate changes in pressure to greatly alter allowing
density and mass transport characteristics of a fluidthe
that largely determine its solvent
power.
Once the drug particles are
they may be recrystallised at solubilised within SCE,
size.Cartbon dioxide and watergreatly reduced particle
are the most
used supercritical fluids. The commonly
SCF process can create
nanoparticulate
in diameter. suspensions particles 5-2000 nm
of
Use of surfactant
Surface active agents
which at low (surfactants) are substances
or interfaces concentrations,
of a
adsorb onto the surfaces
system and alter the surface or
interfacial free energy and the surface or interfacial
tension.
Surface active agents have a
characteristic structure,
possessing both polar (hydrophilic) and non-polar
(hydrophobic) regions in the same molecule.
surfactants are said to be amphipathic in Thus,
nature.
 Depending on their charge
characteristics
active molecules may be anionic, the
sur
cationic, fa ce-
(ampholytic) or non-ionic.
,zwi
Various surfact
Polyglycolized glyceride (Labrasol), t
a
Polyoxyethylene stearates and Tweens, Spans,
er
ntisoniikce
copolymers like )Poly synthetic
(propylene
oxide) - poly (propylene oxide), Poly oxide)-poly (ethylbleoneck
Laspartate), b-poly (ethylene oxide) etc used as
for solubility and dissolution (beta-benzyl.
enhancement. carrier
Improvement of drug ssolubility by using t
the
surfactants is due
between drug and solvent,
tolowering of amphiphilic
surface tension
improvement of wetting
characteristics and micellar solubilization of the dnps
To get any substantial solubility
surfactant concentration must be atenhancement, the
least above the
criticalmicelle concentration (CMC).The CMCwill
depend upon the surfactant itself and the ionic strength is
of the media. Fo
The amount of surfactant needed depends on the
CMCand the degree to which the compound Th

into the surfactant micelles. partitions Se

do
Use of co-solvent
Cosolvent addition is ahighly effective technique for 9)
enhancement of solubility of poorly soluble drugs. It
is well-known that the addition of an organic
cosolvent
to water can dramatically change the solubility of Ansy
drugs.
Weak electrolytes and nonpolar molecules have poor disso
water solubility and it can be improved by altering
polarity of the solvent. This can b¹ achieved by additon
Pre,
of another solvent. This process is knoWn a
cosolvency.
Solvent used to increase solubility is know"
cosolvent. Cosolvent system works by reducing the
interfacial tension between the aqueous solution and
hydrophobic solute.
The use of mixed solvent system is often necessary
Co-
in pharmaceuticals when a drug is poorly ssoluble.
glycerin,
solvents such as ethanol, propylene glycol,glycols,
sorbitol and polyoxyethylene dimethyl
dimethylsulfoxide, ethanol and N, N
formamide can be used.