1. 1 Solution and solubility 3 types of solution a) saturated solution(the solute in solution is in equilibrium with solute in the solid phase.

.) b) unsaturated/ sub-saturated solution(the dissolved solute in a concentration below that necessary for complete saturation at a definite temperature) c) supersaturated solution(contains more of the dissolved solute than it would normally contain at a define temperature, were the undissolved solute present) Solubility can defined in a) quantitative way: concentration of solute in a saturated solution at a certain temperature b) qualitative way: spontaneous interaction of 2 substance to form a homogeneous molecular dispersion. solubility expression of drug: a) X parts of solvent required for one part solute b) moles/ L (The molarity of a solution is the number of moles of solute per liter of solution) c) moles/ g (The molality of a solution is the number of moles of solute per 1000g of solvent) d) %w/v

solvent-solute interactions (like dissolves like principles) a) polar solvent -solubility of a drug is due to the polarity/ dipole moment of the solvent.

-polar solvents dissolve ionic solutes and other polar substances. e-Hildebrand showed that the ability of the solute to form hydrogen bonds is more significant factor than the high dipole moment. Eg: water dissolves phenols, alcohols, aldehydes, ketones, amines, and other oxygen- and nitrogen- containing compounds that can form hydrogen bonds with water. -Other factor affecting the solubility i) acidic and basic character of the constituents in the Lewis electron donor-acceptor ii) structural features ~ ratio of the polar to non-polar groups Eg: when additional polar groups are present, as found in propylene glycol, glycerin and tartaric acid, water solubility increase. ~branching of the carbon chain reduces the nonpolar effect and increase water solubility Eg: tertiary butyl alcohol is miscible with water whereas n-butyl alcohol dissolves to the extent of 8g/100mL of water at 20oC b) non polar solvents - They unable to reduce the attraction between the ions of strong and weak electrolytes because of the solvents low dielectric constants. - They are aprotic solvents that cannot form hydrogen bridges with non-electrolytes, break covalent bonds and ionize weak electrolytes. Hence, ionic and polar solutes are insoluble or slightly soluble in nonpolar solvents. - They can dissolve nonpolar solutes with similar internal pressure through induced dipole interaction. The solute molecules are kept in solution by the weak van der waals forces (London dispersion forces) Eg: Alkaloidal bases and fatty acids can dissolve in non-polar solvents. c) semi-polar solvent -They can induce a certain degree of polarity in non-polar solvent molecules Eg: benzene which is readily polarizable becomes soluble in alcohol -They are intermediate solvents to bring about miscibility of polar and nonpolar liquids.

Eg: Acetone increases the solubility of ether in water (Propylene glycol increase the solubility of water and benzyl benzoate)

1.2 Solubility of liquids in liquids Eg: hydroalcoholic solution = alcohol + water Aromatic water = volatile oils + water Spirit & elixirs = volatile oils + alcohol Collodion = ether + alcohol Varius mixed oil are blended into lotion sprays and medicated oils. 1. Miscibility is the mutual solubilities of the components in liquid-liquid systems. 2. liquid-liquid system can be divided into a) completely miscible -polar and semi-polar solvents (water + alcohol / glycerin + alcohol / alcohol +acetone) are completely miscible because they fix in all proportions. -non-polar solvent (benzene + CCl4) are completely miscible in each other. b) partially miscible

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-solubility can be altered only by intrinsic material property: chemical modification of the molecule - Generally, solubility of a compound depends on the physical and chemical properties of the solute and solvent as well as on such factors as temperature, pressure, pH of the solution and the state of subdivision of the solute. -dissolution can be influenced by extrinsic material property: various chemical, physical or crystallographic (complexation, particle size, surface properties, solid-state modification or solubilization enhancing formulation strategies) 2. thermodynamic solubility of drugs - It is the maximum amount of the most stable crystalline form that remains in solution in a given volume of the solvent at a given temperature and pressure under equilibrium conditions. - it involves an energy balance of a) solvent with solvent b) solute with solute c) solvent and solute. - Thermodynamic equilibrium is achieved when the overall lowest energy state of the system is achieved. (It reflects the balance of forces between the solution and the most stable, lowest energy crystalline form of the solid.)