Chapter 7 Solubility Concepts

how does pressure affect solubility of a gas in a liquid

consider Henry’s law that states solubility of the gas is proportional to pressure of the gas above the solution at equilibrium

how does temperature affect solubility of a gas in a liquid

solubility of gases in liquids decreases as temp increases due to greater tendency of gas to expand and escape from liquid surface

how does presence of salts affect solubility of a gas in a liquid

presence of salts decreases solubility of gases in liquid as it competes for H2O molecules, making H2O less effective at dissolving other substances

how do chemical reactions affect solubility of a gas in a liquid

can lead to chemical increases in solubility

distinguish between complete miscibility, partial miscibility, and practically immiscible

complete- where two liquids are completely soluble in all proportions

partial- where miscibility is a function of temperature (partially soluble liquids)

relatively immiscible- not soluble with each other (oil and water)

what is solubility

concentration of solute present in solvent that occurs at a saturation at a specified temp

what is saturation

solution in which the dissolved solute is in equilibrium with solid solute

what is unsaturated

solution containing dissolved solute at a concentration below that necessary for complete saturation

what is super-saturated

solution containing dissolved solute at a concentration higher than the concentration it would normally contain at a specified temp

define enthalpy, free energy, and entropy

enthalpy- describes amount of heat that is evolved or absorbed as drug goes into solution

free energy- energy within system that is available to do useful work (occurs at any given temperature)

entropy- order or randomness of the system

distinguish between cohesive and adhesive forces

cohesive forces- those that favor solute-solute and solvent-solvent interactions (referred to as crystal lattice enthalpy and always positive because breaking bonds requires energy)

adhesive forces- forces that favor solute-solvent interactions (referred to as solvation enthalpy and always negative because forming bonds uses energy)

how does the US Pharmacopeia and National Formulary list the solubility of drugs

number of mL of solvent in which one gram off solute (drug) will dissolve

in order for dissolution to occur delta G needs to be what

negative

what is the phase solubility analysis

1. this technique can be used to show that a drug is pure

2. identify the presence of impurities

3. estimate the percentage of impurities

phase solubility analysis measures absorbance using what

beer’s law A = epsilon x beta x c

A is absorbance

epsilon is molar absorptivity or extinction coefficient

b is path length

c is concentration

if a increases so does concentration

what can be determined from solubility plot

1. the number of components present

2. the percentage of components present in the sample

3. the solubility of the components

true of false: the substance with the lowest ratio of solubility to fraction present is the first to precipitate in a multi-component system

true

what are exceptions to no break in the line when you plot solubility analysis data

1. when an impurity is present with the same solubility of the drug is present at the same amount

2. when an impurity is present in an amount such that the ratio of the fraction to impurity to fraction of drug is equal to the ratio of the solubility of the impurity to solubility of drug

factors affecting solubility of solids in liquids

1. properties of solute

2. properties of solvent

3. temperature

4. pH

5. cosolvent (adding another solvent)

6. solubilizing agrents (improves solubility)

how does molecular surface area affect solubility

the larger the solute surface area, the larger the hole required in the solvent, and the larger the interaction required between solute and solvent

poorly soluble weak acids are often reacted with what

strong base (sodium hydroxide) if it says sodium salt it’s a weak acid

poorly soluble weak bases are often reacted with what

strong acid (if it says sulfate indicates drug is a weak base)

properties of the solvent

polarity

dielectric constant

capability for hydrogen bonding

solubility parameter of the solvent s

solubility parameter

convenient and one of the best factors for predicting the solubility of a solute in any given solvent

the closer the solubility parameter of the solvent and solute the what

the greater the mutual solubility of the pair

importance of micelles in solubility

their hydrophobic core provides a place for poorly water-soluble drugs to be dissolved and escape from unfavorable solute-solvent interactions present in the aqueous phase