Quantitative approach to the to the factor influcing solubility of drug; (Solubility of drug part-4)s

Quantitative approach to the to the factor influcing solubility of drug; (Solubility of drug part-4)s

• 1.
  IIIrd Semesester B.pharmacy Physical Pharmaceutics-I Unit-I Solubility of drugs(Part-4) (Quantitative approach to the to the factor influcing solubility of drugs) Presented By : Miss. Pooja D. Bhandare (Assistant Professor) Kandhar College of Pharmacy, Nanded
• 2.
   : FACTORINFLUCING SOLUBILITY OF DRUGS 1. TEMPERATURE: • TEMPERATURE WILLAFFECT SOLUBILITY. • GENERALLY, AN INCREASE IN THE TEMPERATURE OF THE SOLUTION INCREASES THE SOLUBILITY OF A SOLID SOLUTE. • IF THE SOLUTION PROCESS ABSORB ENERGY (ENDOTHERMIC) THEN THE SOLUBILITY WILL BE INCREASES AS THE TEMPERATURE IS INCREASED. • IF THE SOLUTION PROCESS RELEASE ENERGY (EXOTHERMIC) THEN THE SOLUBILITY WILL DECRECEASE WITH INCREASING TEMPERATURE. • A FEW SOLID SOLUTES ARE LESS SOLUBLE IN WARM SOLUTION.
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  2. NATURE OFSOLVENT: • POLARITY OF THE BOTH SOLUTE AND SOLVENT 3. THE BOILING POINT OF THE LIQUIDS AND THE MELTING POINT OF SOLIDS: • WE CAN CORRELATIVE SOLUBILITY WITH MELTING POINT AND BOILING POINT. • BOTH THE REFLECT THE STRENGTHS OF INTERACTIONS BETWEEN THE MOLECULES IN THE PURE LIQUID OR THE SOLID STATE. • IN GENERAL, AQUEOUS SOLUBILITY DECREASESTHE INCREASING BOILING POINT AND MELTING POINT. 4.CRYSTAL PROPERTIES: • POLYMORPHS HAVE THE SAME CHEMICAL STRUCTURE BUT DIFFERENT PHYSICAL PROPERTIES, SUCH AS SOLUBILITY, DENSITY, HARDNESS AND COMPRESSION CHARACTERISTICS. • A DRUG THAT EXISTS AS AN AMORPHOUS FORM (NON CRYSTALLINE FORM) GENERALLY DISSOLVES MORE RAPIDLY THAN THE SAME DRUG IN CRYSTALLINE FORM.
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  5. PARTICLE SIZE(SURFACE AREA ) OF DRUG PARTICLES: PARTICLE SIZE SURFACE AREA SOLUBILITY
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  WHERE, S IS THESOLUBILITY OF FINE PARTICLE S0 IS THE SOLUBILITY OF LARGE PARTICLE Γ IS THE SURFACE TENSION OF PARTICLE V IS MOLAR VOLUME T IS THE ABSOLUTE TEMPERATURE R IS THE RADIUS OF FINE PARTICLE R IS THE GAS CONSTANT
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  6. THE INFLUENCEOF SUBSTITUENT’S IN MOLECULAR STRUCTURES : • THE SOLUBILITY OF MOLECULES IN WATER DEPENDS ON ITS INTERACTION WITH WATER MOLECULE. • SUBSTITUENT’S CAN BE CLASSIFIED AS EITHER HYDROPHOBIC OR HYDROPHILIC, DEPENDS ON THEIR POLARITY.  POLAR GROUPS SUCH AS –OH CAPABLE OF HYDROGEN BONDING WITH WATER MOLECULE IMPART HIGH SOLUBILITY. NON POLAR SUCH AS –CH3 ARE HYDROPHOBIC AND IMPACT LOW SOLUBILITY IONISATION OF THE SUBSTITUENT INCREASES SOLUBILITY, E.G., -COOH AND –NH2 ARE SLIGHTLY HYDROPHILIC WHEREAS -COO(-) AND –NH3 ARE VERY HYDROPHILIC.
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  • THE POSITIONOF THE SUBSTITUENT ON THE MOLECULE CAN INFLUENCE ITS EFFECT ON SOLUBILITY SOLU, FOR EXAMPLE THE AQUEOUS SOLUBILITY, FOR EXAMPLE THE AQUEOUS SOLUBILITIES OF O-,M- AND P DIHYDROXYBENZENE.
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  7. MOLECULAR SIZE: •MOLECULAR SIZE AFFECT SOLUBILITY • THE LARGER THE MOLECULE OR THE HIGHER ITS MOLECULAR WEIGHT THE LESS SOLUBILITY THE SUBSTANCE. • LARGER MOLECULE ARE MORE DIFFICULT TO SURROUND WITH SOLVENT MOLECULES IN ORDER TO SOLVATE THE SUBSTANCE. • IN THE CASE OF ORGANIC COMPOUNDS THE AMOUNT OF CARBON BRANCHING WILL INCREASES THE SOLUBILITY SINCE MORE BRANCHING WILL REDUCE THE SIZE (OR VOLUME) OF THE MOLECULE AND MAKE IT EASIER TO SOLVATE THE MOLECULE WITH SOLVENT.
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  8. PH : •IS ONE OF THE PRIMARY INFLUENCES ON THE SOLUBILITY OF THE MOST DRUGS THAT CONTAIN IONIZABLE GROUP. • LARGE NUMBER OF DRUGS ARE WEAK ACID OR WEAK BASE. • SOLUBILITY DEPENDS ON THE DEGREE OF IONIZATION. • DEGREE OF IONIZATION DEPENDS ON PH • ( ABOUT 85 OF MARKETED DRUG CONTAIN FUNCTIONAL GROUPS THAT ARE IONISED TO SOME EXTENT AT PHYSIOLOGICAL PH (PH 1.5-8). • IONIZATION: STRONG- IONIZED AT ALL PHS • WEAK- ONLY IONIZED AT CERTAIN PHS (MOST DRUGS ARE WEAK ACID OR WEAK BASE) • IONIZED DRUG THAT ARE NOT VERY LIPID SOLUBLE-ONLY NON-IONIZED FROM OF DRUG CROSSES MEMBRANE RAPIDLY. • PERCENT IONIZATION IS PH DEPENDENT
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  • PKA ISTHE NEGATIVE LOG OF IONIZATION CONSTANT AND IS EQUAL TO THE PH AT WHICH A DRUG IS 50% IONIZED. • WEAK ACID BECOMES HIGHLY IONIZED AS PH INCREASES. • WEAK BASES BECOME HIGHLY IONIZED AS PH DECREASES. • DEGREE ON IONIZATION DEPENDS ON PH.
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  • ACCORDING TOTHE HENDERSON- HASSELBALCH EUACTION, THE DIFFERENCE BETWEEN THE PH OF THE SOLUTION AND PKA OF THE DRUG IS COMMON LOGARITHIM OF THE RATIO OF IONIZED TO UNIONIZED FROM OF THE DRUG. • FOR ACID DRUGS • LOG(IONIZED/UNIONIZED) = PH – PKA OR WE CAN SAY • RATIO OF IONIZED TO UNIONIZED IS 10*/1 WHERE • * = PH-PKA