Solubility and Solubilization

By
Mahendrasingh Ajitsingh Chavan M.Pharm I st year (pharmaceutics) S.P.C.P. NAGPUR mahendra.chavan3@gmail.com

Definitions
Quantitative term- as the concentration of solute in a saturated solution at a certain temperature. Qualitative term- the spontaneous interaction of two or more substances to form a homogenous molecular dispersion.

Saturated solution - one in which the solute is in equilibrium with the solid phase (solute) Unsaturated or subsaturated solutionone 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 rule

Solubility can be described by using Gibbs phase rule F=CP+2 F = number of degrees of freedom C = 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 SOLVENTS Semipolar 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
Pressure Temperature Present of salt Chemical reaction

EFFECT OF PRESSURE Henrys 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.

HENRYS RELATION---

C2 = P
= inverse of Henrys law constant C2 = concentration of dissolved gas P = 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 --Henrys 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 miscible e.g. polar and semipolar solvent such as water and alcohols, glycerin and alcohol, alcohol and acetone

PARTIAL MISCIBILITY When 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 LIQUIDS

The 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 Hf To - T - log X2i = 2.303R T To

X2i is ideal solubility of the solute T0 is the melting point of the solid solute T is the absolute temperature of solution
NON IDEAL SOLUTIONS The mole fraction solubility of a solute in non ideal solution is expressed Hf To - T + log2 - log X2i = 2.303R TTo

APPROXIMATE SOLUBILITY Term Parts of solvent required for one part of solute Very soluble -less than 1 part Freely soluble -1 to 10 part Soluble -10 to 30 part Sparingly Soluble -30 to 100 part Slightly Soluble -100 to 1000 part Very slightly Soluble -1000 to 10000 part Practically insoluble -more than 10000 part

Micelle Formation

Micelles

aggregates of amphiphilic molecules

Critical Micelle Concentration (cmc)

concentration above which micelles begin to form

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

Surface Tension
Magnitude of Property critical micelle concentration Concentration of Surfactant

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 (nonpolar) reservoir.

nonpolar solute

Properties of Association Colloids

Solubility of nonpolar solute Magnitude of Property

Surface Tension critical micelle concentration

Concentration of Surfactant

"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 (Martins) E SHOTTON , Physical Pharmaceutics C.V.S.SUBRAMANYAM ,Text Book Of Physical Pharmaceutics

Thank you..