This document discusses solubility, including definitions, expressions, mechanisms, factors affecting solubility, and approaches to enhancing solubility. Solubility refers to the property of a solid, liquid, or gas dissolving in a solid, liquid, or gas. It can be expressed quantitatively based on parts of solvent required to dissolve one part of solute. Solubility depends on factors like temperature, pressure, nature of solute and solvent, and can be enhanced through approaches like reducing particle size, modifying crystal habit, using surfactants or complexation, chemical modification of solute, or co-crystallization.

1. SOLUBILITY
PRESENTED BY:- GUIDED BY:-
TARUN POKHARIYAL MISS. STUTI SINGH
M.PHARM.(PHARMACEUTICS) JAIPUR NATIONAL
JAIPUR NATIONAL UNIVERSITY UNIVERSITY (JAIPUR)
JAIPUR
DATE- 29 AUG 2011

2. CONTENTS
 INTRODUCTION
 EXPRESSION OF SOLUBILITY
 MECHENISM OF SOLUBILITY
 SOLVENTS FOR SOLUBILISATION
 SOLUBILITY SYSTEM
 FACTORS AFFECTING SOLUBILITY
 APPROCHES OF SOLUBILITY ENHANCEMENT
 REFERENCES

3. INTRODUCTION:-PROPERTY OF A SOLID, LIQUID
OR GAS TO DISSOLVE IN SOLID, LIQUID OR GAS.
o IN QUANTITATIVE TERM
o IN QUALITATIVE TARM
EXPRESSION OF SOLUBILITY:-
ACCORDING TO USP AS NUMBER OF MILILETRES OF
SOLVENT IN WHICH 1 GRAM OF SOLUTE WILL DISSOLVE

4. TERMS USED PART OF SOLVENT
REQUIRED FOR ONE PART
OF SOLUTE
VERY SOLUBLE LESS THAN 1 PART
FREELY SOLUBLE 1-10 PARTS
SOLUBLE 10-30 PARTS
SPARINGLY SOLUBLE 30-100 PARTS
SLIGHTLY SOLUBLE 100-1000 PARTS
VERY SLIGHTLY SOLUBLE 1000-10000
PRACTICAL Y MORE THAN 10000
INSOLUBLE/INSOLUBLE

5. OTHER TERMS TO EXPRESS THE SOLUBILITY:-
1. MOLARITY
2. MOLALITY
3. %
RELATED TERMS OF SOLUBILITY:-
1. SATURATED SOLUTION
2. SUBSATURATED SOLUTION
3. SUPERSATURATED SOLUTION

6. SOLUBILITY CAN BE DESCRIBED BY THE GIBBS
PHASE RULE AS FOLLOW:-
F=C-P+2
WHERE
F= NO. OF DEGREE FREEDOM
C=SMALLEST NO. OF COMPONENT THAT
DESCRIBE THE CHEMICAL COMPOSITION OF
EACH PHASE
P=NUMBER OF PHASE

7. • HILDEBRAND& SCOTT APPROACH:-
SOLVENT POWER OF A LIQUID IS INFLUENCED BY
ITS INTERMOLECULAR COHESIVE FORCES &
THAT THE STRENGTH OF THESE FORCES.

8. MECHENISM OF SOLUBILITY
SOLUTE –SOLVENT INTERACTION:- FOR THE
SOLUBILIZATION INTERMOLECULAR FORCES MUST
EXIST.
1. REPULSIVE AND ATTRACTIVE FORCES
2. VAN DER WAAL FORCE
3. ION DIPOLE & ION INDUCED DIPOLE
4. HYDROGEN BONDS

9. VAN DER WAAL FORCES:- MOLECULE TEND TO
ALIGN THEMSELVES WITH THEIR NEIGHBOUR SO THAT
NEGATIVE POLE OF ONE MOLECULE POINT TOWARD
THE OPPOSIT
ION DIPOLE AND ION INDUCED DIPOLE:- CATION
ATTRACT THE NEGATIVE OXYGEN ATOM OF WATER
AND ANION ATTRACTING HYDROGEN ATOM OF
WATER MOLECULE
SOLVENTS FOR SOLUBILIZATION:-
• POLAR SOLVENT
• NONPOLAR SOLVENTS
• SEMIPOLAR SOLVENTS

10. • POLAR SOLVENTS:- THESE DISSOLVE IONIC SOLUTES
AND OTHER POLAR SUBSTANCES
MECHENISM:-
I. REDUCE FORCE OF ATTRACTION BETWEEN
OPPOSITELY CHARGED ION IN CRYSTAL.
II. SOLVENTS BREAK COVALENT BONDS OF
POTENTIALLY STRONG ELECTROLYTE BY ACID BASE
REACTION
HCL+H2O H3O +CL⁻
III. FINALLY POLAR SOLVENTS ARE CAPABLE OF
SOLVATING MOLECULES THROUGH DIPOLE
INTERACTION FORCES WHICH LEAD TO SOLUBILITY
OF COMPOUND.

11. • NONPOLAR SOLVENTS:- DISSOLVE NONPOLAR
SOLUTE WITH SIMILAR INTERNAL PRESSURE
THROUGH INDUCED DIPOLE INTERACTION.
eg.oil in benzene
• SEMIPOLAR SOLVENTS:- eg KETONE AND
ALCOHOL.
CAN INDUCE CERTAIN DEGREE OF POLARITY IN
NONPOLAR SOLVENTS.
eg. ACETONE INCREASE SOLUBILITY OF ETHER IN
WATER.

12.  HOLES OPEN IN THE SOLVENT
 MOLECULES OF SOLID BREAK AWAY
FROM THE BULK
FREE MOLECULES INTEGRATED INTO THE
HOLE IN SOLVENT

13. SOLUBILITY OF GASES IN LIQUID:-
eg. AMMONIUM
WATER.
CONC.OF DISSOLVED GAS WHEN IT IS IN
EQUILIBRIUM WITH SOME OF THE PURE GAS ABOVE
THE SOLUTION .
SOLUBILITY OF LIQUIDS IN LIQUIDS:-eg.
ALCOHOL+ WATER=HYDROALCOHOLIC WATER

14. IDEAL OR REAL SOLUTION:-
RAOULT’S LAW
Pi =pi⁰ Xi
where,
pi = partial pressure of component in liquid
pi⁰= vapor pressure in pure state
xi= mole fraction of component in
solution
TWO DEVIATION:-
NEGATIVE DEVIATION:-ADHESIVE ATTRACTION B/W MOLECULE OF
DIFFERENT SPECIES EXCEED THE COHESIVE ATTRACTION B/W LIKE
MOLECULE
POSITIVE DEVIATION:-

15. TYPES OF LIQUIDS –LIQUIDS SYSTEM:-
(1) COMPLETELY MISCIBLE-WATER AND ALCOHOL
(2) PARTIAL MISCIBLE-PHENOL WATER SYSTEM
(3) TERNERY SYSTEM
addition of third compound in the pair of partialy
miscible liquid
CONJUGATE SOLUTIONS:-
CONTAIN TWO LIQUIDS WHICH ARE PARTIALLY
MISCIBLE THAN LAYER OF SATURATED SOLUTION
FORMED IN LITTLE AMOUNT ON THE BORDERLINE
Eg PHENOL IN WATER.
CRITICAL SOLUTION TEMP:-
1. UPPER CONSOLUTE TEMP.phenol water
system(66.8O)
2. LOWER CONSOLUTE TEMP.trietylamine& water
(18.5)

17. FACTORS AFFECTING SOLUBILITY:-
1. PARTICLE SIZE
2. TEMPERATURE-SOLID↑ GAS↓
3. PRESSURE
FOR GAS HENARY LAW:- C=ớP
C= CONC. OF DISSOLVED GAS
P= PARTIAL PRESSURE
SIGMA= SOLUBILITY CONSTANT
4.NATURE OF THE SOLUTE AND SOLVENT
eg.1 GM OF LEAD CHLORIDE DISSOLVE IN 100 gm. Of WATER
AT ROOM TEMP. 200GM OF ZINC CHLORIDE CAN DISSOLVE

18. 5.MOLECULAR SIZE:-
6EFFECT OF CHEMICAL REACTION:-. eg. HCL IS
10000 TIMES MORE SOLUBLE IN WATER THAN IS
OXYGEN
7.POLARITY:-
8.POLYMORPH:-
9.SALTING OUT:-
10.pH.:-as pH increase OF SOLUTION THE
QUANTITY OF DRUG IN SOLUTION INCREASE BCZ
THE WATER SOLUBLE IONIZABLE SALT IS FORMED
HA↔H+ A-

19. APPROACHES OF SOLUBILITY ENHANCEMENT:-
PHYSICAL MODIFICATION.
1. PARTICLE SIZE REDUCTION
I. MICRONIZATION
II. NANO SUSPENSION
2. MODIFICATION OF CRYSTAL HABIT
CRYSTALLINE FORM, AMORPHOUS FORM
ANHYDROUS FORM,HYDRATES
3. DRUG DISPERSION IN CAREEIERS:-
1. EUTECTIC MIXTURE:-poorly soluble drug with
highly water soluble carrier.eg.urea with
chloramphanicol
2. SOLID DISPERSION:drug in an inert carrier. Eg
pvp, polyethylene glycol.
3. SOLID SOLUTION

20. 4.COMPLEXATION:
I. STACHING COMPLEXATION:overlap of planar
region.
II. INCLUSION COMPLEXATION:insertion of
nonpolar molecule into host.eg cyclodextrin
5.BY USING SURFACTANTS:-
I. ANIONIC
II. CATIONIC
III. NONIONIC
6. MICROEMULSION:-IS A FOUR COMPONENT
SYSTEM COMPOSED OF EXTERNAL
PHASE,INTERNAL PHASE,SURFACTANT AND
COSURFACTANT
DROPLET DIAMETER 0.1 MICRON

21. CHEMICAL MODIFICATION:-
1. ADJUST THE PH
2. CHANGE DIELECTRIC CONSTANT
eg.nonionizable and hydrophobic substances
3. USE OF SALT FORM
OTHER TECHNIQUES:-
1.CO-CRYSTALLIZATION- CO-CRYSTALS ARE
CRYSTALLINE MATERIAL THAT CONSIST TWO OR MORE
MOLECULAR (ELECTRICALLY NEUTRAL) SPECIES HELD
TOGETHER BY NON COVALENT FORCES.eg.sacchrin,
nicotinamide ,acetic acid

22. 2. CO-SOLVANCY:-solubilisation of drug into co-
solvent
weak electrolyte and non nonpolar molecules
have poor water solubility can be improve by altering
polarity of solvents.
Solubility enhancement as high as 500 fold achieved
using 20% 2-pyrollidone.
3. HYDROTROPHY:-it increase the solubility in
water due to presence of large amount of additives.
eg. sodium benzoate, urea.

23. 4.SOLUBILISING AGENTS:- eg PEG 400
IMPROVES SOLUBILITY OF HYDROCHLORTHIAZIDE
5.NANOTECHNOLOGY APPROACHES:-
1. NANOCRYSTALS:-particle size 1-1000 nm
2. NANOMORPH

24. REFERENCES
1) PHYSICAL PHARMACY-ALFRED MARTIN
2) REVIEW ARTICLE ( THE PHARMA RESEARCH )
3) ADVANCE PHARMACEUTICS –CHERNG-JUKIM
4) PHYSICAL PHARMACY –DR. SHYAMLA
BHASKARAN
5) MODERN PHARMACEUTICS-GILBERT S.
BANKER
6) AULTON’S PHARMACEUTICS- MICHAEL E.
AULTON

25. 1