4979 solubility and solubilization

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Mahendrasingh Ajitsingh ChavanMahendrasingh Ajitsingh ChavanM.Pharm I st yearM.Pharm I st year(pharmaceutics)(pharmaceutics)S.P.C.P. NAGPURS.P.C.P. NAGPUR

mahendra.chavan3@gmail.commahendra.chavan3@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…..