WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

Mohini et al. World Journal of Pharmacy and Pharmaceutical Sciences

Volume 2, Issue 6, 4558-4572. Review Article ISSN 2278 – 4357

SOLUBILITY ENHANCEMENT BY VARIOUS TECHNIQUES: AN

OVERVIEW

*Mohini S.Patil1, Sheetal Z.Godse1, Dr. R. B.Saudagar2

1
Department of Quality Assurance Techniques, R. G. Sapkal College of Pharmacy, Anjaneri,
Nashik-422213. Maharashtra, India.
2
Department of Pharmaceutical Chemistry, KCT’s R. G. Sapkal College of Pharmacy,
Anjaneri, Nashik.

Article Received on
20 August 2013,
Revised on 21 Sept 2013,
Accepted on 28 October2013
*Correspondence for
Author:
*Mohini S.Patil
Department of Quality
Assurance Techniques, R. G.
Sapkal College of Pharmacy,
Anjaneri, Nashik-422213.
Maharashtra, India.
mohinipatilresearch@gmail.com
ABSTRACT
Solubility is not to be confused with the ability to dissolve or liquefy a
substance, since this process may occur not only because of dissolution
but also because of a chemical reaction. Low aqueous solubility is the
major problem encountered with formulation development of new
chemical entities as well as for the generic development. More than
40% of new chemical entities developed in pharmaceutical industry are
lipophillic and fail to reach the market due to their poor water
solubility. The solubility behavior of drug is the major challenge for
formulation scientist. The present review is devoted to increase the
solubility of poorly water soluble drugs.
Keywords: Solubility Enhancement, BCS Class.

INTRODUCTION
The oral route of drug administration is the most common and preferred method of delivery
due to convenience and ease of administration.3 Orally administered drug is completely
absorbs only when they show fair solubility in gastric medium and such drugs show good
bioavailability. As about 70% of the human body is made up of water, a drug must be soluble
and thus possess an acceptable bioavailability level.4

The drug in the dosage forms is released and dissolves in the surrounding gastrointestinal
fluid to form a solution for easy absorption. This process is solubility limited. Once the drug

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is in the solution form it passes across the membrane of the cell lining the gastrointestinal
tract. This process is permeability limited. Then afterwards the drug is absorbed into systemic
circulation. In the sense, the oral bioavailability of drug is determined by the extent of drug
solubility and permeability.

The drug must first be in solution in order to be absorbed into the blood circulation. If the
solubility of the drug is less than desirable, measures must be taken to improve its solubility
or to use another more soluble drug form. Excipients which are poorly soluble in water might
retard the release of drug into the dissolution medium. Hence the determination of drug and
excipients solubility’s constitutes an important aspect of formulation study.5

SOLUBILITY
Solubility is the property of a solid, liquid, or gaseous chemical substances called solute to
dissolve in a solid, liquid, or gaseous solvent to form a homogeneous solution of the
maximum quantity of solute in a certain quantity of solvent at specified temperature and
perssure.6

Table 1: USP & BP Solubility criteria

Descriptive term Part of solvent required per 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
Practically insoluble >10000

Process of solubilisation7
The process of solubilisation contains three steps:
• The separation of the molecule of the solvent to provide space in the solvent for solute.
• The breaking of intermolecular ionic bonds in the solute.
• The interaction between the solvent and the solute molecule or ion.

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Factors affecting solubilisation4

• Particle size.
• Temperature.
• Pressure.
• Molecular size.
• Nature of solute & solvent.
• Polarity.
• Polymorphs.

Need for solubility enhancement

Drug absorption from the GI tract can be limited by a variety of factors most significant
contributor being poor aqueous solubility and poor membrane permeability of the drug
molecule. When administered an active agent orally it must first dissolve in gastric and/or
intestinal fluids before it can permeate the membranes of the GIT to reach systemic
circulation. Hence, two areas of pharmaceutical research that focus on improving the oral
bioavailability of active agents include; enhancing of solubility and dissolution rate of poorly
water soluble drugs. The BCS is a scientific framework for classifying a drug substance
based on its aqueous solubility and intestinal permeability.8

As for BCS class II & IV drugs rate limiting step is drug release from the dosage form and
solubility in gastric fluid and not the absorption, so increasing the solubility in turn increase
the bioavailability for BCS class II & IV drugs.

Fig 1: BCS classification

Class I Class II
High permeability High permeability
High solubility Low solubility
Class III Class IV
Low permeability Low permeability
High solubility Low solubility

METHODS FOR SOLUBILITY ENHANCEMENT

The enhancement of oral bioavailability of poorly water-soluble drugs remains one of the
most challenging aspects of drug development although salt formation, solubilization, and
particle size reduction have commonly been used to increase the dissolution rate and thereby

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oral absorption and bioavailability of such drugs. Preparation of solid dispersions using water
soluble carriers is yet another popular approach used to improve the oral bioavailability of
poorly water soluble drugs.10

Methods of Solubility Enhancement

• Particle Size Reduction
Conventional methods
Micronization
Nanosuspension
• Hydrotropy
• Cosolvency
• Solubilization by Surfactants
• Solid Dispersion
The fusion (melt) method
The solvent method
Dropping method
• pH adjustment
• High Pressure Homogenization
• Supercritical fluid recrystallization(SCF)
• Sonocrystallisation
• Complexation
Physical Mixture
Kneading method
Co-precipitate method
• Spray Drying
• Inclusion Complex Formation-Based Techniques
Kneading Method
Lyophilization/Freeze-Drying Technique
Microwave Irradiation Method
• Liquisolid technique
• Micro-emulsion
• Self-Emulsifying Drug Delivery Systems
• Neutralization
• Cryogenic Method

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Spray Freezing onto Cryogenic Fluids

Spray Freezing into Cryogenic Liquids (SFL)
Spray Freezing into Vapor over Liquid (SFV/L)
Ultra-Rapid Freezing (URF)
• Polymeric Alteration
• Salt formation

PARTICLE SIZE REDUCTION

The solubility of drug is often intrinsically related to drug particle size as a particle becomes
smaller, the surface area increases. The larger surface area allows a greater interaction with
the solvent which cause increase in solubility.11 By reducing particle size, increased surface
area improves the dissolution properties.

TECHNIQUES OF PARTICLE SIZE REDUCTION

Conventional methods: Conventional methods of particle size reduction, such as
comminution and spray drying, rely upon mechanical stress to disaggregate the active
compound. Particle size reduction is thus permitting an economic,reproducible, and efficient
means of solubility improvement. However, the mechanical forces natural to comminution,
such as milling and grinding, often impart significant amounts of physical stress upon the
drug product which may induce degradation. The thermal stress which may occur during
comminution and spray drying is also a consider when processingof thermo sensitive or
unstable active agents. Only by using traditional methods ofsolubility enhancement it is not
possible to increase the solubility of poorly soluble drugs upto desirable level.

Micronization: Micronization is another conventional technique for the particle size

reduction. Micronization increases the dissolution rate of drugs through increased surface
area; by decreasing particle size, it does not increase equilibrium solubility. Micronization of
drugs is done by milling techniques using jet mill, rotor stator colloid mills and so forth
micronization is not suitable for drugs having a high dose number because it does not change
the saturation solubility of the drug.7

Nanosuspension: This technology is applied to poorly soluble drugs that are insoluble in
both water and oils. A pharmaceutical nanosuspension is biphasic systems consisting of nano
sized drug particles stabilized by surfactants for either oral and topical use or parenteral and
pulmonary administration. The particle size distribution of the solid particles in

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nanosuspensions is usually less than one micron with an average particle size ranging
between 200 and 600 nm.11

HYDROTROPY: Hydrotropy is a solubilization phenomenon whereby addition of large

amount of a second solute results in an increase in the aqueous solubility of existing solute.
Concentrated aqueous hydrotropic solutions of sodium benzoate, sodium salicylate, urea,
nicotinamide, sodium citrate, and sodium acetate have been observed to enhance the aqueous
solubilities of many poorly water-soluble drugs.8

COSOLVENCY: The solubility of poorly soluble drugs in water can be increased by mixing
it with some water miscible solvent in which the drug is readily soluble. This process is
known as cosolvency and the solvent used in combination are known as cosolvent.7
Cosolvent system works by reducing the interfacial tension between the aqueous solution and
hydrophobic solute. It is also commonly known as solvent blending. There is a dramatic
change in the solubility of drugs by addition of organic co-solvent into the water. The co-
solvents are having hydrogen acceptor or donor groups with a small hydrocarbon region. The
hydrophobic hydrocarbon region usually interferes with the hydrogen bonding network of
water which consequently reduces the intermolecular attraction of water while the
hydrophilic hydrogen bonds ensures water solubility.

SOLUBILIZATION BY SURFACTANTS: Surfactants are molecules with distinct polar

and nonpolar regions. Most surfactants consist of a hydrocarbon segment connected to a polar
group. The polar group can be anionic, cationic, zwitterionic or nonionic. When small polar
molecules are added they can accumulate in the hydrophobic core of the micelles. This
process of solubilization is very significant in industrial and natural processes. The addition
of surfactants may decrease the surface tension and increase the solubility of the drug within
an organic solvent.16The use of surfactants to improve the dissolution performance of poorly
soluble drug products is possibly the fundamental, chief, and the oldest method. Surfactants
are the agents whichreduces surface tension and enhance the dissolution of lipophilic drugs in
aqueous medium. The surfactants are also used to stabilize drug suspensions. When the
concentration of surfactants more than their critical micelle concentration (CMC, which is in
the range of 0.05–0.10% for most surfactants), micelle formation occurs which entrap the
drugs within the micelles. This is known as micellization and generally results in enhanced
solubility of poorly soluble drugs.1

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SOLID DISPERSION: Solid dispersion as group of solid products consisting of at least two
different components, generally, a hydrophilic matrix, and a hydrophobic drug. The matrix
can be either crystalline or amorphous. The drug can be isolated molecularly, in amorphous
particles or in crystalline particles. Solid dispersion can also be referred as the dispersion of
one or more active ingredients in an inert matrix at solid state prepared by the melting,
solvent, and melting solvent method.15 The most commonly used hydrophilic carriers for
solid dispersions include polyvinylpyrrolidone, polyethylene glycols, Plasdone-S630. Many
times surfactants may also used in the formation of solid dispersion. Surfactants like Tween-
80, Docusate sodium, Myrj-52, Pluronic-F68 and Sodium Lauryl Sulphate are used.11

TECHNIQUES OF SOLID DISPERSION

The fusion (melt) method: Accurately weighed amounts of carrier(s) are placed in an
aluminum pan on a hot plate and liquefy, with constant stirring, at a temperature of about
60°C. An accurately weighed amount of active drug is incorporated into the melted carrier(s)
with stirring to ensure homogeneity. The mixture is heated until a clear homogeneous melt is
obtained. The pan is then removed from the hot plate and allowed to cool at room
temperature.

The solvent method: Accurately weighed amounts of active drug and carrier(s) are dissolved
in minimum quantities of chloroform in a round-bottom flask. The solvent is removed using a
rotary evaporator. The obtained solid dispersion is transferred on to the aluminum pan and
allowed to dry at room temperature.

Dropping method: A solid dispersion of a melted drug-carrier mixture is pipetted and then
dropped onto a plate, where it solidifies into round particles. The size and shape of the
particles can be influenced by factors such as the viscosity of the melt and the size of the
pipette. Because viscosity is highly temperature dependent, it is very important to adjust the
temperature so that when the melt is dropped onto the plate it solidifies to a spherical shape.8

pH ADJUSTMENT: Poor water soluble drug may potentially dissolve in water by applying
a pH change. To access the solubility of this approach, the buffer capacity and tolerability of
the selected pH are important to consider. Solubilized excipients that increase environmental
pH within the dosage form to a range higher than pKa of weekly acidic drugs increase the
solubility of that drug, those excipients that act as alkalizing agents may increase the
solubility of weekly basic drugs.15

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HIGH PRESSURE HOMOGENIZATION: High-pressure homogenization has been used

to prepare nanosuspension of many poorly water soluble drugs. In this method, the
suspension of a drug and surfactant is forced under pressure through a nanosized aperture
valve of a high pressure homogenizer. The principle of this method is based on cavitation in
the aqueous phase. The cavitations forces within the particles are sufficiently high to convert
the drug microparticles into nanoparticles. The concern with this method is the need for small
sample particles before loading and the fact that many cycles of homogenization are
required.1

SUPERCRITICAL FLUID RECRYSTALLIZATION(SCF): Those fluids are referred to

as supercritical fluids which are having temperature and pressure greater than its critical
temperature and critical pressure so as they are acquire properties of both gas and liquid. The
best example of this is carbon dioxide. SCF are highly compressible at critical temperatures
and allows alteration in density and mass transport characteristics which determines its
solvent power due to moderate changes in pressure. As the drug gets solubilized within SCF
they can be recrystallized with reduced particle size of drug.13

SONOCRYSTALLISATION: Recrystallization of poorly soluble materials using liquid

solvents and antisolvents has also been employed successfully to reduce particle size. The
novel approach for particle size reduction on the basis of crystallization by using ultrasound
is Sonocrystallisation. Sonocrystallisation utilizes ultrasound power characterised by a
frequency range of 20–100 kHz for inducing crystallization. It’s not only enhances the
nucleation rate but also an effective means of size reduction and controlling size distribution
of the active pharmaceutical ingredients. Most applications use ultrasound in the range 20
kHz-5 MHz.16

COMPLEXATION: Complexation of drugs with cyclodextrins has been used to enhance

aqueous solubility and drug stability. Cyclodextrins of pharmaceutical relevance contain 6, 7
or 8 dextrose molecules (α, β, γ-cyclodextrin) bound in a 1,4-configuration to form rings of
various diameters. The ring has a hydrophilic exterior and lipophilic core in which
appropriately sized organic molecules can form noncovalent inclusion complexes resulting in
increased aqueous solubility and chemical stability.12Complexation relies on relatively weak
forces such as London forces, hydrogen bonding and hydrophobic interactions.16

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TECHNIQUE OF COMPLEXATION
Physical Mixture: Active drug with suitable polymer in different ratios mixed in a mortar for
about one hour with constant trituration. The mixture is passed through sieve no. 80 and
stored in dessicator over fused calcium chloride.

Kneading Method: Active drug with suitable polymer in different ratios is added to the
mortar and triturated with small quantity of ethanol to prepare a slurry. Slowly the drug is
incorporated into the slurry with constant trituration. The prepared slurry is then air dried at
250C for 24hrs. The resultant product is pulverized and passed through sieve no. 80 and
stored in dessicator over fused calcium chloride.

Co-precipitate Method: Active drug is dissolved in ethanol at room temperature and

suitable polymer is dissolved in distilled water. Different molar ratios of active drug and
suitable polymers are mixed respectively. The mixture is stirred at room temperature for one
hour and the solvent is evaporated. The resultant mass is pulverized and passed through sieve
no. 80 and stored in a desiccators

SPRAY DRYING: The solvent evaporation of drug and polymer solution in different ratio is
carried out by using spray dryer. The solutions are prepared by dissolving drug in methanol
and polymer in distilled water and mix both solutions, which produces a clear solution. The
solvent evaporated by using evaporator. The spray dried mixture of drug with polymer is
obtained in 20–30 min.8

INCLUSION COMPLEX FORMATION-BASED TECHNIQUES

Among all the solubility enhancement techniques, inclusion complex formation technique has
been employed more precisely to improve the aqueous solubility, dissolution rate, and
bioavailability of poorly water soluble drugs. Inclusion complexes are formed by the
insertion of the nonpolar molecule or the nonpolar region of one molecule (known as guest)
into the cavity of another molecule or group of molecules (known as host). The most
commonly used host molecules are cyclodextrins.1 The cavity of host must be large enough to
accommodate the guest and small enough to eliminate water, so that the total contact between
the water and the nonpolar regions of the host and the guest is reduced.16 Solid inclusion
complexes are prepared by various methods such as kneading method co-precipitation,
neutralization, co-grinding, spray drying method, and microwave irradiation method.15

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TECHNIQUES OF INCLUSION COMPLEX METHOD

Kneading Method: This method is based on impregnating the CDs with little amount of
water or hydroalcoholic solutions to convert into a paste. The drug is then added to the above
paste and kneaded for a specified time. The kneaded mixture is then dried and passed through
a sieve if required. In laboratory scale, kneading can be achieved by using a mortar and
pestle. In large scale, kneading can be done by utilizing the extruders and other machines.
This is the most common and simple method used to prepare the inclusion complexes and it
presents very low cost of production.

Lyophilization/Freeze-Drying Technique: In order to get a porous, amorphous powder with

high degree of interaction between drug and CD, lyophilization/freeze drying technique is
considered suitable. In this technique, the solvent system from the solution is eliminated
through a primary freezing and subsequent drying of the solution containing both drug and
CD at reduced pressure. Thermolabile substances can be successfully made into complex
form by this method. The limitations of this technique are the use of specialized equipment,
time consuming process, and yield poor flowing powdered product. Lyophilization/freeze
drying technique is considered as an alternative to solvent evaporation and involve molecular
mixing of drug and carrier in a common solvent.1

Microwave Irradiation Method: This technique involves the microwave irradiation reaction
between drug and complexing agent using a microwave oven. The drug and CD in definite
molar ratio are dissolved in a mixture of water and organic solvent in a specified proportion
into a round bottom flask. The mixture is reacted for short time of about one to two minutes
at 60 ºc in the microwave oven. After the reaction completes, adequate amount of solvent
mixture is added to the above reaction mixture to remove the residual, uncomplexed free drug
and CD. The precipitate so obtained is separated using whatman filter paper, and dried in
vacuum oven at 40 ºc for 48 hrs.14

LIQUISOLID TECHNIQUE: The liquisolid technique is a novel concept where a liquid

may be transformed into a free flowing, readily compressible and apparently dry powder by
simple physical blending with selected carrier and coating material. The liquid portion, which
can be a liquid drug, a drug suspension or a drug solution in suitable non-volatile liquid
vehicles, is incorporated into the porous carrier material. Once the carrier is saturated with
liquid, a liquid layer is formed on the particle surface which is instantly adsorbed by the fine

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coating particles. Thus, an apparently dry, free flowing, and compressible powder is
obtained.17

MICRO-EMULSION: A micro emulsion is an optically clear pre-concentrate, isotropic,

thermo dynamically stable transparent (or translucent) system, containing a mixture of oil,
hydrophilic surfactant and hydrophilic solvent which dissolves a poorly water soluble drug.
Upon contact with water, the formulations spontaneously disperse (or ‘self emulsifies’) to
form a very clear emulsion of exceedingly small and uniform oil droplets containing the
solubilized poorly soluble drug. Micro-emulsions have been employed to increase the
solubility of many drugs that are practically insoluble in water, along with incorporation of
proteins for oral, parenteral,as well as percutaneous/transdermal use.

SELF-EMULSIFYING DRUG DELIVERY SYSTEMS: Self-emulsifying or self-micro

emulsifying systems use the concept of in situ formation of emulsion in the gastrointestinal
tract. The mixture of oil, surfactant, co-surfactant, one or more hydrophilic solvents and co-
solvent forms a transparent isotropic solution that is known as the self-emulsifying drug
delivery system (SEDDS).18 Self-emulsifying drug delivery systems (SEDDS) and
selfmicroemulsifying drug delivery systems (SMEDDS) are isotropic solutions of oil and
surfactant which form oil-in-water microemulsions on mild agitation in the presence of water
(Shah et al., 1994). The poorly soluble drug can be dissolved in a mixture of surfactant and
oil which is widely known as preconcentrate. These novel colloidal formulations on oral
administration behave like oil-in-water microemulsions. Compared with ready-to-use
microemulsions, the SEDDS and SMEDDS have been shown to improve physical stability
profile in long term storage.20

NEUTRALIZATION: Drug is added in alkaline solution like sodium hydroxide,

ammonium hydroxide. A solution of β- Cyclodextrin is then added to dissolve the joined
drug. The clear solution obtained after few seconds under agitation is neutralized using HCl
solution until reaching the equivalence point. At this moment, the appearance of a white
precipitate could be appreciated, corresponding to the formation of the inclusion compound.
The precipitate is then filtered and dried.19

CRYOGENIC METHOD: Cryogenic techniques have been developed to enhance the

dissolution rate of drugs by creating nanostructured amorphous drug particles with high
degree of porosity at very low-temperature conditions. Cryogenic inventions can be defined

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by the type of injection device (capillary, rotary, pneumatic, and ultrasonic nozzle), location
of nozzle (above or under the liquid level), and the composition of cryogenic liquid
(hydrofluoroalkanes, N2, Ar, O2, and organic solvents). After cryogenic processing, dry
powder can be obtained by various drying processes like spray freeze drying, atmospheric
freeze drying, vacuum freeze drying, and lyophilisation.

TECHNIQUES OF CRYOGENIC METHOD

Spray Freezing onto Cryogenic Fluids: Briggs and Maxvell invented the process of spray
freezing onto cryogenic fluids. In this technique, the drug and the carrier (mannitol, maltose,
lactose, inositol, or dextran) were dissolved in water and atomized above the surface of a
boiling agitated fluorocarbon refrigerant. Sonication probe can be placed in the stirred
refrigerant to enhance the dispersion of the aqueous solution.

Spray Freezing into Cryogenic Liquids (SFL): The SFL particle engineering technology
has been used to produce amorphous nanostructured aggregates of drug powder with high
surface area and good wettability. It incorporates direct liquid-liquid impingement between
the automatized feed solution and cryogenic liquid to provide intense atomization into
microdroplets and consequently significantly faster freezing rates. The frozen particles are
then lyophilized to obtain dry and free-flowing micronized powders.

Spray Freezing into Vapor over Liquid (SFV/L): Freezing of drug solutions in cryogenic
fluid vapours and subsequent removal of frozen solvent produces fine drug particles with
high wettability. During SFV/L the atomized droplets typically start to freeze in the vapor
phase before they contact the cryogenic liquid. As the solvent freezes, the drug becomes
supersaturated in the unfrozen regions of the atomized droplet, so fine drug particles may
nucleate and grow.

Ultra-Rapid Freezing (URF): Ultra-rapid freezing is a novel cryogenic technology that

creates nanostructured drug particles with greatly enhanced surface area and desired surface
morphology by using solid cryogenic substances. Application of drugs solution to the solid
surface of cryogenic substrate leads to instantaneous freezing and subsequent lyophilization
(for removal of solvent) forms micronized drug powder with improved solubility. Ultra rapid
freezing hinders the phase separation and the crystallization of the pharmaceutical ingredients
leading to intimately mixed, amorphous drug-carrier solid dispersions, and solid solutions.1,7

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POLYMERIC ALTERATION: Different crystalline forms of a drug that may have

different properties are known as Polymorphs. Polymorphs may differ in physicochemical
properties such as physical and chemical stability, shelf-life, melting point, vapor pressure,
intrinsic solubility, dissolution rate, morphology, density and biological activities as well as
bioavailability. Amongst the stable, unstable and metastable crystalline polymorphs,
metastable forms are associated with higher energy with increased surface area, subsequently
solubility, bioavailability and efficacy. With regard to bioavailability, it is preferable to
change drug from crystal forms into metastable or amorphous forms. However, the possibility
of a conversion of the high energy amorphous or metastable polymorph into a low energy
crystal form having low solubility cannot be ruled out during manufacture and storage. It is
preferable to develop the most thermodynamically stable polymorph of the drug to assure
reproducible bioavailability of the product over its shelf-life under a variety of real-world
storage conditions.19

SALT FORMATION: Dissolution rate of particular salt is usually different from that of
parent compound. Sodium and potassium salt of week acid dissolve more rapidly than that of
pure salt. Limitation of salt formation includes epigastric distress due to high alkalinity,
reactivity with atmospheric water and carbon dioxide leads to precipitation, patient
compliance and commercilation.15

CONCLUSION
The various techniques enlisted in this articleare used in combination for solubility
enhancement of poorly water soluble drugs, but the solubility improvement mainly depends
on the selection of proper method. The selection of suitable method for solubility
enhancement is depends on drug properties like melting point, solubility, chemical nature,
physical nature, pharmacokinetic behaviour and so on. The article concludes that solubility of
poorly water soluble drugs is an important concept to reach into systemic circulation to show
its pharmacological response.

REFERENCES
1. Savjani KT, Gajjar AK, Savjani JK, Drug solubility: Importance and Enhancement
Techniques.
Available from:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399483/

www.wjpps.com 4570
Mohini et al. World Journal of Pharmacy and Pharmaceutical Sciences

2. Sharma D, Soni M, Kumar S, Gupta GD, Solubility Enhancement-Eminent Role in

Poorly Soluble Drugs, Research Journal of Pharmacy and Technology.2(2);April-
June.2009:220-224.
3. Nikam SP, A Review: Increasing Solubility of Poorly Soluble Drugs, by Solid Dispersion
Technique. Research Journal of Pharmacy and Technology.4(12);Dec.2011:1933-1940.
4. Chauhan NN, Patel NV, Suthar SJ, Patel JK, Patel MP. Micronization of BCS-II Drugs
By Various Approaches For Solubility Enhancement-A Review. Research Journal of
Pharmacy and Technology.5(8);Aug.2012:999-1005.
5. Pardhi D, Shivhare U, Suruse P, Chabra G. Lquisolid Technique For Solubility
Enhancement of Poorly Water Soluble Drugs. Research Journal Pharmaceutical Dosage
Forms and Technology.2(5);Sept-Oct.2010:314-322.
6. Lachman L, Lieberman HA, The Theory and Practice of Industrial Pharmacy, CBS
Publication & Distributors Pvt. Ltd. Special Indian Edition 2009: 221.
7. Md. MofizurRahman, Abul Bashar Ripon Khalipha, Jamal Ahmed, Md.
AbShuaibRafshanjani, ShanjidaHaque, Methods of Solubility And Dissolution
Enhancement For Poorly Water Soluble Drugs: A Review,1-23.
8. Pawar AR, Choudhari PD, Novel Techniques For Solubility, Dissolution Rate and
Bioavailability Enhancement of Class II & IV drugs, Asian Journal of Biomedical &
Pharmaceutical Science(13)2012,9-14.
9. Varshney HM, Chatterjee A. Solubility Enhancement of Poorly Hydrophilic Drugs by
Using Different Newer Techniques: A Review. International Journal of Therapeutic
Applications. Volume-6,2012:8-13.
10. Mukhija U, Soni N, Chawla A, Bhatt DC, Physical Properties and Dissolution Behaviour
of Meloxicam/Poloxamer Solid Dispersions Prepared By Hot Melt Method and
Microwave Assisted Method. International Journal of Research In Pharmacy and
Science(2)April-june.2012.64-74.
11. Kumar A, Sahoo SK, Padhe K, Kochar PPS, Satpathy A, Pathak N. Review On Solubility
Enhancement Techniques ForHydrophbic Drugs. PharmacieGlobale International Journal
Of Comprehensive Pharmacy.2(3)2011.1-7.
12. Vemula VR, Lagishetty V, Lingala S. Solubility Enhancement Techniques. International
Journal of Pharmaceutical Sciences Review and Research(1);Nov-Dec2010:41-51.
13. Md. Sajid A, Choudhary V. Solubility Enhancement Methods WithImportance of
Hydrotropy. Journal of Drug Delivery and Therapeutics(6);2012:96-101.

www.wjpps.com 4571
Mohini et al. World Journal of Pharmacy and Pharmaceutical Sciences

14. Patil JS, Kadam DV, Marapur SC, KamalapurMV.Inclusion Complex System; A Novel
Technique To Improve The Solubility And Bioavailability Of Poorly Soluble Drugs: A
Review. International Journal of Pharmaceutical Sciences Review And
Research.2(2);May-June2010.29-34.
15. Sareen S, Mathew G, Joseph L. Improvement In Solubility of Poor Water-Soluble Drugs
By Solid Dispersion. International Journal of Pharmaceutical Investigation: Review
Article.2(1);2012:12-17.
16. Mohanachandran PS, Sindhumol PG, Kiran TS. Enhancement of Solubility and
Dissolution Rate: An Overview. PharmacieGlobale International Journal of
Compehensive Pharmacy.1(4);2010:1-10.
17. Doijad RC, Pathan AB, Gaikwad SS, Baraskar SS, Pawar NB, Maske VD. Liquisolid: A
Novel Technique For Dissolution Enhancement of Poorly Soluble Drugs. Current Pharma
Research. 3(1);2012:735-749.
18. Chaudhary A, Nagaich U, Gulati N, Sharma VK, Khosa RL. Enhancement of
Solubilization and Bioavailability of Poorly Soluble Drugs By Physical and Chemical
Modification: A Recent Review. Journal of Advanced Pharmacy Education and
Reseach.2(1);2012:32-67.
19. Thorat YS, Gonjari ID, Homani AH. Soubility Enhancement Techniques: A Review On
Conventional and Novel Approaches. International Journal of Pharmaceutical Sciences
and Research.2(10);2011:2501-2513.
20. Yellla SR Krishnalah. Pharmaceutical Technologies for Enhancing Oral Bioavailability of
Poorly Soluble Drugs, Inventi Spreading knowledge.10-18.

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