A co solvent system is one in which a water miscible or partially miscible organic solvent is mixed with water to form a modified aqueous solution. And the phenomenon called Cosolvency cosolvents 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.

1. Solubility Enhancemeny By
Co-solvency
Mr. Sagar Kishor Savale
[Department of Pharmaceutics]
avengersagar16@gmail.com
2015-2016

2. Content
 Introduction
 Methods of expressing solubility & concentration
 Solubility of solids in liquids
-Factors affecting solubility of solids in liquids
 Solubility of liquids in liquids
 Solubility of gases in liquids
 Solubility solids in solids
 Cosolvency
 Theory
 Effect of cosolvency
 Applications
 Advantages
 Disadvantages
 Conclusion
 References
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3. Introduction1:-
Solubility:
‘Solubility of a substance in a solvent at given temperature and
pressure is the amount of substance that has been passed into solution
form when an equilibrium is attained between solution and undissolved
substance’.
Also, it is the spontaneous interaction of two OR more substance to
form a homogeneous molecular dispersion.
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4. Methods for expressing solubility & concentration1,2:-
 Quantity per Quantity: simply on weight and volume basis,
contained in given solution;
i.e.1kg m-3 = 1gm L-1 ,1kg in 1 litre etc.
 percentage:
concentration in % w/v = weight. of solute *100
volume of solvent
 Parts: used to described strength of solution, the certain parts by
weight(gm) of solid are contained in given no. of given parts by
volume(ml) e.g. 1mg 1000ml =1ppm.
 Molarity: no of moles of solute contained in dm3 unit mole L-1
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5. Cont’ed …
 molality:- no. of moles of solutes divided by the mass of the
solvent(kg). SI unit is mol kg-1
 Mole fraction :- no. of moles of solutes divided by the total no. of
moles of solutes and solvent.
x = n1
n1+n2
 Miliequivalents:- no. of milimoles in 1litre
(1milimole = 1000 a mole )
1 miliEq = ionic wt. (mg)
valency
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6. Prediction of solubility1:-
A compound can dissolves in particular solvent of similar chemical properties
of the solvents
‘LIKE DISSOLVES LIKE’
i.e. polar in polar and vice-versa.ss
 Quantitative description of solubility-
Description Approx wt. solvent to dissolve 1gm of solute
Very soluble <1
Freely soluble 1-10
Soluble 10 -3o
Sparingly soluble 30-100
Slightly soluble 100-1000
Very slightly soluble 1000-10000
Practically insoluble >10000
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7. Solubility determination5:-
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 Solubility is normally depends on temperature, so temperature is
recorded in each solubility measurement.
 Plot of solubility against temperature is commonly used for solubility
determination.
 Two methods are available for determination are as follow.
I. Analytical method
II. Synthetic method
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8. Hildebrandt & scott solubility parameter1:-
this explains that, solvent power of liquid influenced by its
intermolecular cohesive forces, and the forces called as Hildebrandt
solubility parameter.
- it provides quantitative prediction of
some Hydrocarbons, Non-polar and
Non reacting liquids.
 Temperature:-
some compounds shows the increasing solubility with rise in temp.
e.g KNO3 between 0-50 oC ,Na2SO4 up to 35oC but not after it.
Factors affecting the solubility of solids in liquids:-
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9. Effect of temperature1,3,4:-
 MOLECULAR STRUCTURE OF SOLUTE:-
e.g phenol
 Nature of solvent:-
e.g diazepam, metronidazol etc.
 Solute/solid characteristics:
i.e crystal str. Particle size etc.
 pH:- affects degree of ionization
& further absorption.
Common ion effect:-
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10. Solubility of gases in liquids1,4:-
According to Henry’s law,
‘At constant temperature, The solubility of gases in liquids is directly
proportional to the pressure of the gas above the liquid’.
w = k .p
Solubility of solids
in solids:- simple
Eutectic mixture, physical
dispersion
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11. Co-solvency2,3:-
CO-SOLVENT :-
A cosolvent system is one in which a water miscible or partially
miscible organic solvent is mixed with water to form a modified
aqueous solution. And the phenomenon called Cosolvency
 cosolvents 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.
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12. Theory of Co-solvency3:-
Solubility of a non-electrolyte solute in any solvent can be expressed
by general eqn.
Log X = -ΔHf/2.303RT.Tm (Tm-T)-Log y
where, Log X =solutes mole fraction solubility
ΔHf = molar heat of fusion
R,T= constant
y = activity coefficient
where, C11 = cohesive energy of solvent
C22 = cohesive energy of solute
C12 = adhesive energy
Log y = C11 + C22 -2C12
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13. Selection of cosolvent3,4:-
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.
These biological effects depends upon various factors as;
 Dose or concentration in formulation
 Routes of administration
 Rate of administration
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14. Effect of solvent on stability of drug3:-
Depends on, Concentration of cosolvent, nature of reactants in systems ,
transition state of reactants & its concentration
Consider; for the reaction between an ion and a dipolar molecule,
Log kε2 =Log kε1-Zµe cosø/2.303RTkr2( 1/ε2-1/ε1)
where, µ = dipole moment
ø = angle between resultant dipole & axis of collision of
two species
k1,k2 = reaction rate constant of two different solvents
ε = dielectric constant
r = distance between two ions
T = absolute temperature
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15. Cont’ed…
If both are ions,
Log kε2 = Log kε1- Z1.Z 2 e/2.303KTr (1/ε2 - 1/ε1 )
where, Z1 ,Z 2 = ionic charge
for the dipolar species,
Log kε2 = Log kε1- 2µ1. µ2/2.303KTr3 (1/ε2 - 1/ε1 )
From this mathematical eqn. We conclude that,
Acceleration OR deacceleration of reaction rate upon a change in
solvent - polarity, dipolar distance, reactants
Hence, water involves in instability of drugs.
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16. Products containing cosolvent system3:-
Dosage form Drug Cosolvents
Parenteral Diazepam Ethanol up to 30%
Parenteral Etoposide PEG 300 (65%), ethanol
30%
Ophthalmic Chloramphenicol PEG 300
Topical Erythromycin Ethanol 50-70%
Topical 5-Fluorouracil Propylene glycol
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17. Applications3 :-
 Ultimate role in solubility enhancement of poorly water soluble
drugs.
 Improvement in absorption and bioavailability.
 Apart from increasing solubility, it have importance in
improvement solubility of volatile constituents used to impart a
desirable flavour and odour to the product.
 Solubility considerations at dosage form design.
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18. Limitations3:-
1] Potential biological effects:-
A. hemolytic effect -
B. local effect- DMSO 10-300mg irritable, muscle damage
-propylene glycol
- Renal and CNS effects in mice
2] Intolerance:-
incompliance by pediatric patients
3] Cosolvent related parameters:-
- many are reported for initiating OR catalyzing oxidative
degradation e.g. PEGs
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19. Cont’ed….
- Cosolvents may contains heavy metal impurities such other
- For Parenteral products, Dimethylacetamide is widely used. But
in case of oral liquids its application is limited, because of its
objectionable odour and taste.
- DMSO demonstrated for the skin permeation enhancement
property but not approved for dermal preparations.
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20. Conclusion:-
 Solubility enhancement by cosolvent 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
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21. References:-
1] Aultons Pharmaceutics ‘Design And Manufacture Of Medicines’
Edited By M.E. Aulton, Published By Elsevier Pharmaceutical
Sciences,2oo7, 3rd Edition; Page No.23-29
2] Remington's ‘Pharmaceutical Sciences’ Edited By A.R.Gennero ,Mack
Publishing Company1985 ,18th Edition; Page No.207-215
3] ‘Encyclopedia Of Pharmaceutical Technology’, 2007,By Informa
Healthcare Usa Inc. Page No.806
4] Cooper And Gunn‘s, ‘Tutorial Pharmacy’ Edited By
S.J.Carter,2005,CBS Publishers & Distributors ,6th Edition; Page
No.8-12
5] The Pharmaceutical Codex, Principles And Practices Of
Pharmaceutics, Edited By Walter Lund ,2009,CBS Publishers &
Distributors,12th Edition ;Page No.43-48
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22. …!
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THANK YOU