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Solubility.seminar

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  • 1. SOLUBILITYPRESENTED BY:- GUIDED BY:-TARUN POKHARIYAL MISS. STUTI SINGHM.PHARM.(PHARMACEUTICS) JAIPUR NATIONALJAIPUR 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 TERMo IN QUALITATIVE TARMEXPRESSION OF SOLUBILITY:- ACCORDING TO USP AS NUMBER OF MILILETRES OFSOLVENT IN WHICH 1 GRAM OF SOLUTE WILL DISSOLVE
  • 4. TERMS USED PART OF SOLVENT REQUIRED FOR ONE PART OF SOLUTEVERY SOLUBLE LESS THAN 1 PARTFREELY SOLUBLE 1-10 PARTSSOLUBLE 10-30 PARTSSPARINGLY SOLUBLE 30-100 PARTSSLIGHTLY SOLUBLE 100-1000 PARTSVERY SLIGHTLY SOLUBLE 1000-10000PRACTICAL Y MORE THAN 10000INSOLUBLE/INSOLUBLE
  • 5. OTHER TERMS TO EXPRESS THE SOLUBILITY:-1. MOLARITY2. MOLALITY3. %RELATED TERMS OF SOLUBILITY:-1. SATURATED SOLUTION2. SUBSATURATED SOLUTION3. SUPERSATURATED SOLUTION
  • 6. SOLUBILITY CAN BE DESCRIBED BY THE GIBBSPHASE RULE AS FOLLOW:- F=C-P+2WHEREF= NO. OF DEGREE FREEDOMC=SMALLEST NO. OF COMPONENT THAT DESCRIBE THE CHEMICAL COMPOSITION OF EACH PHASEP=NUMBER OF PHASE
  • 7. • HILDEBRAND& SCOTT APPROACH:-SOLVENT POWER OF A LIQUID IS INFLUENCED BYITS INTERMOLECULAR COHESIVE FORCES &THAT THE STRENGTH OF THESE FORCES.
  • 8. MECHENISM OF SOLUBILITYSOLUTE –SOLVENT INTERACTION:- FOR THESOLUBILIZATION INTERMOLECULAR FORCES MUSTEXIST.1. REPULSIVE AND ATTRACTIVE FORCES2. VAN DER WAAL FORCE3. ION DIPOLE & ION INDUCED DIPOLE4. HYDROGEN BONDS
  • 9. VAN DER WAAL FORCES:- MOLECULE TEND TOALIGN THEMSELVES WITH THEIR NEIGHBOUR SO THATNEGATIVE POLE OF ONE MOLECULE POINT TOWARDTHE OPPOSITION DIPOLE AND ION INDUCED DIPOLE:- CATIONATTRACT THE NEGATIVE OXYGEN ATOM OF WATERAND ANION ATTRACTING HYDROGEN ATOM OFWATER MOLECULESOLVENTS FOR SOLUBILIZATION:-• POLAR SOLVENT• NONPOLAR SOLVENTS• SEMIPOLAR SOLVENTS
  • 10. • POLAR SOLVENTS:- THESE DISSOLVE IONIC SOLUTES AND OTHER POLAR SUBSTANCESMECHENISM:-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. AMMONIUMWATER. CONC.OF DISSOLVED GAS WHEN IT IS INEQUILIBRIUM WITH SOME OF THE PURE GAS ABOVETHE 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 solutionTWO DEVIATION:-NEGATIVE DEVIATION:-ADHESIVE ATTRACTION B/W MOLECULE OFDIFFERENT SPECIES EXCEED THE COHESIVE ATTRACTION B/W LIKEMOLECULEPOSITIVE 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 partialymiscible liquidCONJUGATE SOLUTIONS:-CONTAIN TWO LIQUIDS WHICH ARE PARTIALLYMISCIBLE THAN LAYER OF SATURATED SOLUTIONFORMED 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)
  • 16. FACTORS AFFECTING SOLUBILITY:-1. PARTICLE SIZE2. TEMPERATURE-SOLID↑ GAS↓3. PRESSURE FOR GAS HENARY LAW:- C=ớPC= CONC. OF DISSOLVED GASP= PARTIAL PRESSURESIGMA= SOLUBILITY CONSTANT4.NATURE OF THE SOLUTE AND SOLVENT eg.1 GM OF LEAD CHLORIDE DISSOLVE IN 100 gm. Of WATERAT ROOM TEMP. 200GM OF ZINC CHLORIDE CAN DISSOLVE
  • 17. 5.MOLECULAR SIZE:-6EFFECT OF CHEMICAL REACTION:-. eg. HCL IS10000 TIMES MORE SOLUBLE IN WATER THAN ISOXYGEN7.POLARITY:-8.POLYMORPH:-9.SALTING OUT:-10.pH.:-as pH increase OF SOLUTION THEQUANTITY OF DRUG IN SOLUTION INCREASE BCZTHE WATER SOLUBLE IONIZABLE SALT IS FORMED HA↔H+ A-
  • 18. APPROACHES OF SOLUBILITY ENHANCEMENT:-PHYSICAL MODIFICATION.1. PARTICLE SIZE REDUCTIONI. MICRONIZATIONII. NANO SUSPENSION2. MODIFICATION OF CRYSTAL HABITCRYSTALLINE FORM, AMORPHOUS FORMANHYDROUS FORM,HYDRATES3. DRUG DISPERSION IN CAREEIERS:-1. EUTECTIC MIXTURE:-poorly soluble drug with highly water soluble carrier.eg.urea with chloramphanicol2. SOLID DISPERSION:drug in an inert carrier. Eg pvp, polyethylene glycol.3. SOLID SOLUTION
  • 19. 4.COMPLEXATION:I. STACHING COMPLEXATION:overlap of planar region.II. INCLUSION COMPLEXATION:insertion of nonpolar molecule into host.eg cyclodextrin5.BY USING SURFACTANTS:-I. ANIONICII. CATIONICIII. NONIONIC6. MICROEMULSION:-IS A FOUR COMPONENTSYSTEM COMPOSED OF EXTERNALPHASE,INTERNAL PHASE,SURFACTANT ANDCOSURFACTANTDROPLET DIAMETER 0.1 MICRON
  • 20. CHEMICAL MODIFICATION:-1. ADJUST THE PH2. CHANGE DIELECTRIC CONSTANTeg.nonionizable and hydrophobic substances3. USE OF SALT FORMOTHER TECHNIQUES:-1.CO-CRYSTALLIZATION- CO-CRYSTALS ARECRYSTALLINE MATERIAL THAT CONSIST TWO OR MOREMOLECULAR (ELECTRICALLY NEUTRAL) SPECIES HELDTOGETHER BY NON COVALENT FORCES.eg.sacchrin,nicotinamide ,acetic acid
  • 21. 2. CO-SOLVANCY:-solubilisation of drug into co-solvent weak electrolyte and non nonpolar moleculeshave poor water solubility can be improve by altering polarity of solvents.Solubility enhancement as high as 500 fold achievedusing 20% 2-pyrollidone.3. HYDROTROPHY:-it increase the solubility inwater due to presence of large amount of additives.eg. sodium benzoate, urea.
  • 22. 4.SOLUBILISING AGENTS:- eg PEG 400IMPROVES SOLUBILITY OF HYDROCHLORTHIAZIDE5.NANOTECHNOLOGY APPROACHES:-1. NANOCRYSTALS:-particle size 1-1000 nm2. NANOMORPH
  • 23. REFERENCES1) PHYSICAL PHARMACY-ALFRED MARTIN2) REVIEW ARTICLE ( THE PHARMA RESEARCH )3) ADVANCE PHARMACEUTICS –CHERNG-JUKIM4) PHYSICAL PHARMACY –DR. SHYAMLA BHASKARAN5) MODERN PHARMACEUTICS-GILBERT S. BANKER6) AULTON’S PHARMACEUTICS- MICHAEL E. AULTON
  • 24. 1