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
Apart from as a co-solvent, give five other uses for glycerol in pharmaceutical preparations
Lubricant Humectant Laxative Topically Antibacterial
What are polyethylene glycols (PEGs)?
Long chain polyethers
What are lower MW PEGs used for?
Co-solvents in oral liquids and solid capsules, and eyedrops
What are solid PEGs used for?
Ointment bases
Tablet binders
Film coatings
Lubricants
What are PEGs the basis of?
A number of laxatives e.g. macrogol containing products
- movicol
- polyethylene glycol 3350
- SoftLax
- MiraLax
- GlycoLax
What is used for bowel preparation before surgery or colonoscopy?
Whole bowel irrigation (polyethylene glycol with added electrolytes)
What is PEGylation?
Attachment of PEG to peptides, proteins and antibody fragments to alter physiochemical properties
What are the advantages of PEGylation?
- improved drug solubility
- reduced dosage frequency, toxicity
- extended circulating life
- increased drug stability
- protection from proteolytic degradation
What is PEGASYS?
PEGylated interferon alpha 2a
- used in the treatment of chronic hepatitis C and hepatits B
What is PEGintron?
PEGylated interferon alpha 2b
- used in the treatment of chronic hepatitis C and hepatitis B
What is pH manipulation?
Changing the pH of a solution to change the physical chemistry of a drug by adding or removing protons at certain sites of a molecule
Which pharmacokinetic parameter can be used to choose the correct pH in pH manipulation?
pKa or pKb
How is the pH of a solution adjusted?
- addition of an acid (HCl) or a base (NaOH) as appropriate
- addition of a buffer
What is a buffer solution?
Used as a means of keeping pH at a nearly constant value in a wide variety of pharmaceutical and research applications
How is a buffer made?
An aqueous solution consisting of a mixture of a weak acid and its conjugate base (or a weak base and its conjugate acid)
What happens to a buffer (weak acid and conjugate base) when acid is added to it?
The equilibrium shifts to the left, in accordance with Le Chatelier’s principle
Why does a buffer resist changes in pH?
The hydrogen ion concentration increases by less than the amount expected for the quantity of strong acid added
Do all buffers have the same pH working ranges?
no ;)
What is PBS?
Phosphate Buffered Saline
What is PBS used for?
A buffer solution used in biological and formulation research
Why is pH 7.4 PBS frequently used?
Isotonic
Non-toxic
Used to model bloodstream environment in drug permeation experiments across membranes
Useful as a diluent in cell and tissue culture work
What is an oil molecule typically comprised of?
Glycerol and 2 or 3 free fatty acids (FFAs) derived from plant or animal sources
What is mineral oil?
Any of various colourless, odourless, light mixtures of higher alkanes from a mineral source, particularly a distillate of petroleum
What is a volatile/essential oil?
Mixture of small organic molecules, often with a distinctive aroma and taste
what is paraffin wax ?
Paraffin wax(orpetroleum wax) is a soft colorless solid
derived from petroleum,that consists of a mixture of
long-chainalkanes (typically C20-C40).
It is a highly lipophilic waxy solid at room temperature
and melts at 37°C
describe the properties of mineral oil
Mineral oilis a lipophilic, complex mixture of higher alkanes, typically >C9, and cycloalkanes,typically a distillate of petroleum.
The term ‘mineral oil’ by itself is imprecise, other names, similarly imprecise, include ‘white oil’, ‘paraffin oil’, ‘liquid paraffin’ (a highly refined medical grade),paraffinum liquidum, and ‘liquid petroleum’.
describe the role of an emulsifying ointment
Emulsifying ointment is a viscous mixture of mineral oils. It is used to moisturise very dry skin eg eczema.It is greasy and sticky andleaves a thin layer of oil on the surface of the skin that stops water evaporating. This results in a soothing, softening and moisturising effect.
describe the properties of bees wax
Beeswax is a natural wax produced in the bee hive of honey bees of the genus Apis. It is a highly lipophilic mixture of esters of fatty acids and various long chain alcohols. Pharmaceutical grade Beeswax is pale yellow, smooth, highly refined wax with emollient, soothing and softening properties
describe the properties of ointments
Ointmentsare viscous, greasy, semisolid preparations, often containing either functional ingredients.
Typicalointment basescomprisepetrolatumand mineral oil, or petrolatum and waxy/fatty alcohol combinations
The ratio and grades of these components being selected to give the desired finished product viscosity/spreadability.
Theointment baseneeds to be heated to above its melting temperature prior to the incorporation of active ingredients, whilst mixing.
Eg hydrocortisone
Proprietary ointment bases are
available eg emulsifying ointment BP
