This document provides an overview of solubility enhancement and cosolvency. It begins with definitions of solubility enhancement and cosolvency as using water-miscible solvents to increase the solubility of weak electrolytes and nonpolar molecules. Common cosolvents like ethanol, propylene glycol, and polyethylene glycol are discussed. The mechanisms of how cosolvents increase solubility by changing dielectric constant and promoting hydrogen bonding are explained. Several methods for solubility enhancement are reviewed, including particle size reduction, use of surfactants, solid dispersions, and pH adjustment. The document concludes that various techniques can be combined to improve solubility of poorly soluble drugs based on their properties, with the goal of improving bioavailability

1. PRESENTED BY:MADHAVEE BORADE
UDER GUIDANCE OF: MADHURI GITE
SHRI R.D.BHAKT COLLEGE OF
PHARMACY,JALNA
Review On:Solubility
Enhancement & Cosolvancy

2. CONTENTS
 INTRODUCTION
 REVIEW LITERATURE
 METHOD OF SOLUBLITY ENHANCEMENT
 STUDY OF COSOLVENCY
 THEORY OF COSOLVENCY
 CONCLUSION
 REFERENCE

3. INTRODUCTION
STUDY OF COSOLVENCY
DEFINITION:
The solubility of weak electrolytes and nonpolar molecules can be increased by the addition of water-
miscible solvents. This process is known as co-solvency or solvent blending, and the solvents used in
combination to increase the solubility of the solute are called co-solvents.
COSOLVENTS:
Co solvents have some degree of hydrogen bond donating and or hydrogen bond accepting ability as well
as small hydrocarbon regions.
The resulting solution will have physical properties that are intermediate to that of the pure organic
solvent and water through the reduction of water-water interaction
Example: Ethanol, propylene glycol, glycerin, sorbitol and polyethylene glycol.
Mechanism:
1) change the dielectric constant.
DC of a good co-solvent: 25-80.
2) hydrogen bonding in two solvents

4. REVIEW LITERATURE
 1. S.K. dash et al(2012) [12] : solubility enhancement of poorly poorly water
drugs. Crit Rev Ther Drug Carrier Syst. 2002; 19:553-585.
2. Chellos N.et al(2012)[13]: “cosolvency and soluility enhancement”
Pharmatech 2003, 160-166. They had developed simultaneous determination of
sitagliptin phospate monohydrate and metformin by ultra performance liquid
chromatographic (uplc)method. the chromographic sepreation was achieved on
aquity uplc BEH C8 100 X 2.1mm,1.7 m, colunm using a buffer consisting of 10
mM potassium dihydrogen phosphate and 2 nm hexane 1-sufonic acid sodiun,
salt(PH adjusted to 5.50 with diluted phosphoric acid) and acetonitrile as organic
solvent in a gradient program. The flow rate was 0.2 ml min-1 and the detection
wavelength was 210nm.the limit of detection (LOD) was 0.2 and 0.06 g ml-
1,respectively.the limit of quantification (LOD)was 0.7 and 0.2g ml-
1,respectively.this method was validated with respect to linearity,
accuracy,precision ,specificity,and robustnes soluble drugs . . Crit Rev Ther Drug
Carrier Syst. 2002; 19:553-585.

5. Properties of co-solvents
 co-solvent increases the solubility of a drugs.
 An ideal co-solvents should provide values of dielectric
constant between 25 to 80.
 The most widely used system that will cover this range is a
water.
 It should not cause toxicity or irritancy when administrated for
oral or parental use.
Selection of co-solvent
 Some characteristics of co-solvent which are considered at selection:
 1. Biocompatible
 2. It must be non-toxic. Non-irritating.
 3. It should be able to solubilize the drug in given solvent.
 4. It should be able to cross the membrane.
 5. does not have potential systemic effects.

6. Applications
1. Ultimate role in solubility enhancement of
poorly water soluble drugs.
2. Improvement in absorption and bioavailability.
3. Apart from increasing solubility, it have
importance in improvement solubility of
volatile constituents used to impart a desirable
flavor and odour to the product.
4. Solubility considerations at dosage form design.

7. Commonly used co-solvent
 Glycerol
 PEG400
 Dimethyl Acetamide
 N-Octanol
 Glycerol
 Dimethyl Sulfoxide
 Propylene Glycol
Co-solvent used in Drugs
 Diazepam
 Benzocaine

8. Advantages
 Simple and rapid to formulate and produce.
 Solvents may be combined with other solubilization techniques
and and pH adjustment to further increase solubility of
poorly soluble compounds.
Disadvantage:
 As with all excipients, the toxicity and tolerability related with the
level of solvent administer not to be considered.
 Uncontrolled precipitation occurs upon dilution with aqueous
media. The precipitates may be amorphous or crystalline and can
vary in size.
 Many of the insoluble compounds shares works which are
unsuited to co-solvents alone, particularly for intravenous
administration.
 This is because the drug are extremely insoluble in water and do
not readily re-dissolve after precipitation from the co-solvent
mixture.
 In these situations there is potential risk for embolism and local
adverse effects at the injection site.

9. SOLUBILITY ENHANCEMENT BY VARIOUS
TECHNIQUES: AN OVERVIEW
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
Table : USP & BP Solubility criteria
Descriptive term Part of solvent required per part of solute
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.

10.  PROCESS OF SOLUBILISATION
 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

11. FACTORS AFFECTING SOLUBILISATION
1. Particle size
2. Temperature
3. Pressure
4. Molecular Size
5. Polarity
6. Polymorphs
7. Nature of solute & solvent.

12. NEED FOR SOLUBILITY
ENHANCEMENT
Class I Class II
High permeability
High solubility
High permeability
Low solubility
Class III Class IV
Low permeability
High solubility
Low permeability
Low solubility
Fig 1: BCS classification

13. METHODS OF SOLUBILITY
ENHANCEMENT
• Particle Size Reduction
Conventional methods
Micronization
Nano suspension
• Hydrotropic
• Co-solvency
• Solubilization by Surfactants
• Solid Dispersion
The fusion (melt) method
The solvent method
Dropping method
• pH adjustment
• High Pressure Homogenization
• Supercritical fluid recrystallization(SCF)
• Sonocrystallisation

14. • Complexion
Physical Mixture
Kneading method
Co-precipitate method
• Spray Drying
• Inclusion Complex Formation-Based Techniques
Kneading Method
Lyophilization Freeze-Drying Technique
Microwave Irradiation Method
• Liquid solid technique
• Micro-emulsion
• Self-Emulsifying Drug Delivery Systems
• Neutralization
• Cryogenic Method
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

15. CONCLUSION
The various techniques enlisted in this article are 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 behavior 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.
Solubility enhancement by co-solvent system gives new approaches for
design and formulation of new dosage forms of poor aq. Soluble drugs.
It also helps in improving:
 Bioavailability of drugs
 Stability of drugs

16. REFERENCES
1. Lachman L, Lieberman HA, The Theory and Practice of Industrial Pharmacy, CBS
Publication & Distributors Pvt. Ltd. Special Indian Edition 2009: 221.
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. Lquid solid Technique For Solubility
Enhancement of Poorly Water Soluble Drugs. Research Journal Pharmaceutical Dosage
Forms and Technology.2(5);Sept-Oct.2010:314-322
6.Md. Sajid A, Choudhary V. Solubility Enhancement Methods With Importance of
Hydrotropy. Journal of Drug Delivery and Therapeutics(6);2012:96-101..

17. THANK YOU…