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

CONTENTS INTRODUCTION

EXPRESSION OF SOLUBILITY

MECHENISM OF SOLUBILITY

SOLVENTS FOR SOLUBILISATION

SOLUBILITY SYSTEM

FACTORS AFFECTING SOLUBILITY

APPROCHES OF SOLUBILITY ENHANCEMENT

REFERENCES

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

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 YINSOLUBLE/INSOLUBLE

MORE THAN 10000

OTHER TERMS TO EXPRESS THE SOLUBILITY:-1. MOLARITY

2. MOLALITY

3. %

RELATED TERMS OF SOLUBILITY:-

1. SATURATED SOLUTION

2. SUBSATURATED SOLUTION

3. SUPERSATURATED SOLUTION

SOLUBILITY CAN BE DESCRIBED BY THE GIBBS PHASE RULE AS FOLLOW:-

WHERE

F= NO. OF DEGREE FREEDOM

C=SMALLEST NO. OF COMPONENT THAT

DESCRIBE THE CHEMICAL COMPOSITION OF

EACH PHASE

P=NUMBER OF PHASE

F=C-P+2

• HILDEBRAND& SCOTT APPROACH:-

SOLVENT POWER OF A LIQUID IS INFLUENCED BY ITS INTERMOLECULAR COHESIVE FORCES & THAT THE STRENGTH OF THESE FORCES.

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

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

• 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 SOLUBILITYOF COMPOUND.

• 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.

HOLES OPEN IN THE SOLVENT

MOLECULES OF SOLID BREAK AWAY FROM THE BULK

FREE MOLECULES INTEGRATED INTO THE HOLE IN SOLVENT

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

IDEAL OR REAL SOLUTION:-

RAOULT’S LAW

where,

pi = partial pressure of component in liquidpi⁰= vapor pressure in pure statexi= 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:-

Pi =pi⁰ Xi

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 partialymiscible liquid

CONJUGATE SOLUTIONS:-CONTAIN TWO LIQUIDS WHICH ARE PARTIALLY MISCIBLE THAN LAYER OF SATURATED SOLUTION FORMED IN LITTLE AMOUNT ON THE BORDERLINEEg PHENOL IN WATER.CRITICAL SOLUTION TEMP:-1. UPPER CONSOLUTE TEMP.phenol water

system(66.8O)2. LOWER CONSOLUTE TEMP.trietylamine& water

(18.5)

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

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-

APPROACHES OF SOLUBILITY ENHANCEMENT:-PHYSICAL MODIFICATION.1. PARTICLE SIZE REDUCTIONI. MICRONIZATION II. NANO SUSPENSION2. MODIFICATION OF CRYSTAL HABITCRYSTALLINE 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. Egpvp, polyethylene glycol.

3. SOLID SOLUTION

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

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

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.

4.SOLUBILISING AGENTS:- eg PEG 400

IMPROVES SOLUBILITY OF HYDROCHLORTHIAZIDE

5.NANOTECHNOLOGY APPROACHES:-1. NANOCRYSTALS:-particle size 1-1000 nm

2. NANOMORPH

REFERENCES1) 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

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