4979 solubility and solubilization
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ByBy
Mahendrasingh Ajitsingh ChavanMahendrasingh Ajitsingh ChavanM.Pharm I st yearM.Pharm I st year(pharmaceutics)(pharmaceutics)S.P.C.P. NAGPURS.P.C.P. NAGPUR
[email protected]@gmail.com
Solubility and Solubility and SolubilizationSolubilization
DefinitionsDefinitions
Quantitative term-Quantitative term- as the as the concentration of solute in a concentration of solute in a saturated solution at a certain saturated solution at a certain temperature.temperature.
Qualitative term-Qualitative term- the spontaneous the spontaneous interaction of two or more interaction of two or more substances to form a homogenous substances to form a homogenous molecular dispersion.molecular dispersion.
Saturated solution - one in which the solute is in equilibrium with the solid phase (solute)
Unsaturated or subsaturated solution- one containing the dissolved solute in a concentration below the necessary for complete saturation at definite temperature.
Supersaturated solution – one that contains more of the dissolved solute than it would normally contain at a definite temperature, were the undissolved solute present.
The phase ruleSolubility can be described by using
Gibbs phase rule F = C – P + 2F = number of degrees of freedomC = smallest number of component
that adequate to describe the chemical composition of each phase
P = number of phases
US pharmacopoiea & national formulary states that solubility of drugs as the number of mililiter of solvent in which 1 g of solute will dissolve.
Solvent solute interaction-
-- POLAR SOLVENT-- NON POLAR SOLVENT-- SEMI POLAR SOLVENT
POLAR SOLVENT-- solubility of a drug is due in large
measure to the polarity of the solvent i.e. to its dipole moment.
-- polar solvent dissolve ionic solute and other polar substances.
-- accordingly, water mixes in all proportions with alcohol and dissolves sugars and other polyhydroxy component.
HILDEBRAND showed that ability of the solute to form hydrogen bonds is a far more significant factor than is polarity as reflected in high dipole moment.
--water dissolves phenols, alcohols, aldehyde, ketons , amines , and other oxygen and nitrogen containing compound that can form hydrogen bonds with water
H H R---O-----H---O--- alcohol
Polar solvent such as water act as solvent according following mechanisms---
owing to their high dielectric constant , namely about 80 for water
polar solvent break covalent bonds of potentially strong electrolytes by acid- base reaction cause these solvents are amphiprotic.
HCl + H2O H3O + Cl
NON POLAR SOLVENTS Non polar solvents are unable to
reduce the attraction between the ions of strong and weak electrolytes because of solvents low dielectric constant.
They belong to group aprotic solvents
Non polar compound can dissolve non polar solutes with similar internal pressure through induced dipole interaction.
SEMI POLAR SOLVENTSSemipolar solvents can induce a certain
degree of polarity in nonpolar solvent molecules.e.g. ketones, alcohols
benzene which is readily polarizable becomes soluble in alcohol
In fact, semipolar compound can act as intermediate solvent to bring miscibility of polar and non polar liquids.e.g. propylene glycol increase the mutual solubility of water and peppermint oil and of water and benzyl benzoate
SOLUBILITY OF GASES IN LIQUIDS
The solubility of a gas in a liquid is the concentration of the dissolved gas when it is in eqlibrium with some of the pure gas above the solution.
Solubility depend on PressureTemperaturePresent of salt Chemical reaction
EFFECT OF PRESSUREHenry’s law in a very dilute solution
at constant temperature the concentration of dissolved gas is proportional to the partial pressure of the gas above the solution equilibrium
Partial pressure of the gas is obtained by substracting the vapor pressure of the solvent from the total pressure above solution.
HENRY’S RELATION---
C2 = σP
σ = inverse of Henry’s law constantC2 = concentration of dissolved gasP = pressure ( partial )
EFFECT OF TEMPERATURE ---As the temperature increases solubility of
most gases decreases.Owing to the greater tendency of the gas to
expand.Salting out Gases are often liberated from solutions in
which they are dissolved by the introduction of on electrolyte such as NaCl and sometimes by a non electrolyte such as sucrose. This phenomenon known as SALTING OUT.
EFFECT OF CHEMICAL REACTION ---
Henry’s law applies strictly to gases that are only slightly soluble in solution and that do not react in any way in solvent.
Gases such as HCl , ammonia, CO2 shows deviation as result of chemical reaction between gas and solvent.
SOLUBILITY OF LIQUIDS IN LIQUIDS ---Two or more liquids are mixed together in
the preperation of pharmaceutical solution.
e.g. hydroalcoholic solution, aromatic water etc
LIQUID-LIQUID SYSTEM--- Complete miscilbility--- solvents which are mix in all proportions
said to by completely misciblee.g. polar and semipolar solvent such as
water and alcohols, glycerin and alcohol, alcohol and acetone
PARTIAL MISCIBILITYWhen certain amounts of water and ether
or water and phenol are mixed, two liquid layer are formed , each containing some of the other liquid in the dissolved state.
a) The mutual solubilities of the partially miscible liquids are influenced by temperature.
INFLUENCE OF FOREIGN SUBSTANCES- The addition of substance to binary liquid
system produces a ternary system.
If added substance, soluble in only one or if the solubilitites in the two liquids are markedly different , the liquid pair is decreased.
when the third substances is soluble in both of the liquids to roughly the same extent the mutual solubility of the liquid pair is increased.
The upper critical solution temperature is lowered and a lower critical solution temperature raised.
SOLUBILITY OF SOLIDS IN LIQUIDSThe most important type of
pharmaceutical solutions.The solubility of the solids in liquid can
predicated for only ideal solutions. equation derived from thermodynamic
considerations for an ideal solution of a solid in a liquid is
ΔHf To - T - log X2i = 2.303R T To
X2i is ideal solubility of the solute T0 is the melting point of the solid soluteT is the absolute temperature of solution
NON IDEAL SOLUTIONSThe mole fraction solubility of a solute in non
ideal solution is expressed ΔHf To - T + logϒ2 - log X2i = 2.303R TTo
APPROXIMATE SOLUBILITYTerm Parts of solvent required for one part of soluteVery soluble -less than 1 partFreely soluble -1 to 10 partSoluble -10 to 30 partSparingly Soluble -30 to 100 partSlightly Soluble -100 to 1000 part Very slightly Soluble -1000 to 10000 partPractically insoluble -more than 10000 part
Micelles– aggregates of amphiphilic molecules
Critical Micelle Concentration (cmc)– concentration above which micelles
begin to form
Micelle Formation
Solution of Amphiphiles
Concentration of surfactant below the critical micelle concentration.
Solution of Amphiphiles
Concentration of surfactant below the critical micelle concentration.
Solution of Amphiphiles
Concentration of surfactant below the critical micelle concentration.
Association Colloids
Concentration above the critical micelle concentration.
Properties of Association Colloids
Magnitude of Property
Concentration of Surfactant
Surface Tension
critical micelle concentration
Solubility of non-polar solutes
Concentration of surfactant below the critical micelle concentration.
nonpolar solute
Micellar Solubilization
The interior of the micelle represents a hydrocarbon (non-polar) reservoir.
nonpolar solute
Properties of Association Colloids
Magnitude of Property
Concentration of Surfactant
Surface Tension
critical micelle concentration
Solubility of nonpolar solute
"Official" Products
Saponated Cresol Solution NF XIII– 49% V/V cresol solubilized in a
concentrated soap solution
Hexachlorophene Liquid Soap USP– 0.24% W/W hexachlorophene solubilized in
an 11% potassium soap solution
References
PATRICK J. SINKO, Physical Pharmacy And Pharmaceutical Sciences (Martin’s)
E SHOTTON , Physical PharmaceuticsC.V.S.SUBRAMANYAM ,Text Book Of
Physical Pharmaceutics
Thank you…..