Solubility Phenomena Flashcards
Solution Def.
Mix of 2+ components forming homogenous phase down to molecular levels (pariticles<1nm)
Solubility Def.
Max conc of substance that will dissolve in give solution (usually water) volume at given temp
Are suspensions considered to have solubility
No. Substance must dissolve (have interactions at molecular level)
Dissolution Def.
Rate at which substance goes from solid state to solution in given solvent
Types of Solutions
Liquid-liquid (eg elixirs), solid-liquid, solid-solid (melting and resolidifying, gas-gas (anaesthetics, require high pressure), gas-liquid (HCl)
Solvent Def.
Component solute dissolves in, determines phase. Different polarities between solvents (eg water and ethanol). Considereed an excipient in dosage form
Solute
Dissolving Agent. Can be drug or excipient
Saturated Solution
Max dissolved solute has been reached. Equilibrium is reached between solute dissolved and being returned to solid state.
Measuring Solubility
No instruments. Measurably adding excess solute to solution of known volume at a fixed temperature
Concentration vs Solubility Expression
Concentration is solute in solution. Solubility is solute in solvent
Milliequivalents per Litre
mg equivilant weights of solute per litre of solution
Osmole Def.
1 mole of osmatic substance
Formation of Solution Outline
Increase in entropy (disorder) and increase in attractive forces
Free Energy Outline (delta G)
When free energy is negative there is chance a reaction will spontaneously happen. Factors are Heat Change, Change in Temperature abd change in entropy
Relationship between heat change(enthalpy) and free energy
The bigger the heat change the more positive the free energy (low chance of rection occuring)
Relationship Temp and Free energy
The bigger the temp = the more negative free energy
Relationship Change in entropy (disorder) and free energy
The higher the entropy = the more negative the free energy
Endothermic Dissolution Outline
Heat absorbed during dissolution(solution cools). Increase temp = increase solubility. More energy used when bonds are broken then formed. Drug doesn’t have enough heat
Exothermic Dissolution Outline
Releases heat during dissolution (solution warms). Increased temp = decreased solubility. More energy used when bonds are formed not broken
Can substances change dissolution type
Yes. Sodium sulfate decahydrate begins endothermic nut converts to exothermic as it loses water
Unsaturated solution Def.
Conc of dissolved solute is less then required for saturation at given temp. Made more in practice to account for evapouration
Supersaturated Solution Def.
Contains more dissolved solute then could normally contain at given temp. Not thermodynamically stable (precipitates to saturated)
Hydrophilic (lipophobic) Solutes
Polar substance soluble in water and other polar substances. Bonds with water to form aqueous solution
Hydrophobic (lipophilic) Solutes
Non-polar substance soluble in non-polar solvents. have low aqueos solubility
Polar Solvents Outline
Consists of strong dipolar molecules. Has H bonding. Eg water
Semipolar Solvents Outline
Strong dipolar molecules. Dipole bonds (no H bonds) eg acetone
Non-polar solvents
Small/ no dipole character eg benzene
Amphoteric Def.
Substances that can be positively and negatively charged
Anionic Substances
Weak and strong acids
Cationic Substances
Weak and strong bases
Zwitterion Def.
Molecule that can hold both positive and negative charge at the same time Eg amino (positive) acids (negative)
Relationship between pH, counter ions and ionisation
Ionisation of weak electrolytes (eg weak acid/base) is controlled by pH and counter ions. Ionisation is reversible
Dissociate Def.
To break apart
Electrolyte Def.
Substances that dissociate into constitutive ions when dissolved in suitable solvent. Dissociation results in ionisation leaving electrolytes conductive of electricity
Strong Electrolytes Def.
Substances undergoing complete dissociation
Weak Electrolytes Def.
Substance undergoing partial dissociation
Non-electrolytes def.
Non-ionic substance that don’t dissociate
How to increase dissociation
Add salt to compound
adding electrolytes to electrolyes in solution
increases di-electric constant = increase solubility
Adding a very soluble electrolyte to a non-electrolyte (or visa-versa)
Di-electric constant decreases. Solubility of substance in original solution decreases
How electrolyres effect the solubility of non
Salting out (organic substances precipitate) or Salting In (organic substances more soluble (less frequent)
Miscible Def
2 substances form homogenous molecular sol. when mixed in any proportion. Works in all states but is mainly liquids
Partial Miscible Def.
2 substance form homogenous molecular sol when mixed in specific proportions at specific temp and pressure
Immiscibility
A negligible amount of 2 substances mix to form solution. Results in emulsions
What substances chemical composition make them more hydrophillic
OH, conjugate acid and conjugate base
What substances are the lipophilic
organic compounds (carbon chains)
Log S Outline
Intrinsic Solubility
Tm Outline
Melting point. Increased Tm = decreased log S
Log P Outline
Partition coefficent (drug conc in non-polar solvent divided by conc in polar (in same container)). Measures whether substance would dissolve in polar (eg water) or non-polar (eg octanol) concentration. As log P increases, log S decreases. If log P is positive it’s lipophilic if logP is negative it’s hydrophilic
What does Log P = x or Log P = -x mean
Substance is 10^x times more likely to dissolve in octanol/water
Brick Dust Def.
Stable crystalline materials with strong intermolecular bonds. Low aqueous solubility
Grease Balls Def.
Highly lipophilic drugs unable to form bonds with water
Log P Drug development
Drugs Log P <0.5 are water soluble. Predicts ability to permeate membranes, correlation for drugs ability to bind to proteins (lipophilic bind), activity of preservatives and drug adsorption behaviour
Why do differnt cells have different optimal Log P
Their barriers require different powers of permeation eg skin 1-4, ophtalmic (cornea) 1-2 and small intestine 1-5
POlarity Test of solvent
High Performance Chromotography
What can help reduces the reuired log P of drug
If cell contains complementary transporters and concentration gradients
Solvent Def.
Liquid in which solute dissolves to form solution
Polarity def.
Measure of electric distribution within molecule. Measured by dipole moment (distance opposite charges are seperated)
Dielectric Constant Def.
Measure of ease vehicle/medium seperates opposite charges. Ratio of material capacitance to reference. Polar = high, non-polar = low
Polar Solvation Mechanisms
Dipole moments, dielectric constant and H bonding potential
Non-polar Solvation Mechanisms
Unabke to seperate ions of strong and weak electrolytes. Dissolves non-polar substance by induced dipoles and solute kept disperesed in solution via Van der Waals
