PH2107 - solutions 2.1 Flashcards
Why are some drugs very poorly soluble in a chosen solvent to the point where therapeutically useful concentrations are unobtainable?
- insoluble in vehicle of choice (typically water)
- tight crystalline structure
- tightly bound ion-counterion salts (low Kdiss)
What factor determines which strategy is used to increase aqueous solubility?
Whether a true solution is desired or a disperse phase is suitable
What two methods are used to increase aqueous solubility?
Co-solvency
pH manipulation
What is cosolvency?
The solubility of a weak electrolyte or a non-polar compound can be improved by addition of a water miscible solvent
What is the most widely used co-solvent system?
Water/ethanol blend
Apart from water/ethanol blend, what other co-solvency systems are used?
Glycerol
Propylene glycol
Sorbitol
Syrup
How is a co-solvent system set up?
A solution is made in primary solvent (the one in which the drug is most soluble)
Secondary (and maybe tertiary) solvents are introduced, but below the level at which the drug precipitates
Describe water as a molecule
Non-ionic, polar molecule
Describe water as a solvent
Water is a good solvent for other polar or charged compounds:
- salts
- sugars
- acids
- alkalis
- some gases
- oxygen
- carbon dioxide (carbonation)
What type of substances dissolve in water?
Hydrophilic substances
What type of substances do not mix well with water?
Hydrophobic substances
Which substance forms the base solvent in the majority of liquid pharmaceutical preparations?
Water
Why is water the most widely used solvent in pharmaceuticals?
- lack of toxicity
- physiological compatibility
What are the four grades of water used in pharmaceuticals?
- Potable water - tap water, suitable for drinking
- Purified water BP - prepared by distillation or deionisation of drinkable water. Freshly boiled and cooled
- Water for injections BP - for parenteral solutions. Sterilisation of pyrogen free distilled water
- Water for injections BP without CO2 or air - for drugs sensitive to CO2 e.g. aminophylline
Which alcohols are used as a co-solvent?
Low C are very good solvents:
- ethanol
- methanol
- propanol / isopropyl alcohol
- butanol
- propylene glycol (PG)
- glycerol / glycerine
Why is ethanol used as a solvent or co-solvent?
Miscible with water and many organic fluids
Widely used solvent
Common solvent in formulations
What is the problem with using methanol, propanol, isopropyl alcohol or butanol as a co-solvent?
Toxic
Apart from toxicity, what is another problem with using butanol as a co-solvent?
Less hydrophilic
What is the advantage of using propylene glycol (PG) in formulations?
Less volatile