Oral Solutions Flashcards
What is a solution?
A mixture of two or more components that form single homogenous phase at molecular level
What is a solute?
Components dispersed as molecules or ions in solvent
What is a solvent?
Liquid capable to dissolve a substance + usually major component in a solution + determine phase of system
Is a solution optically clear?
YES
What are the advantages of solutions?
Fast onset of action
Dose uniformity assured = doesn’t need shaking
Vol of liquid dose can be measure accurately
Easy to swallow
Easy to manufacture
What are the disadvantages of solutions?
Increased drug instability compared to solid state
Some liquids require cold storage to maintain shelf-life
Many drugs poorly soluble in H2O
Liquids bulky to carry
Packaging costs higher
What are the oral solution properties?
Stable throughout shelf-life Palatable: flavouring + colouring added Appropriate viscosity for palatability + pourability At physiological pH where possible Dose in multiples pf 5ml for convenience
What is the most solvent?
H2O
Why is H2O most common solvent?
Lack of toxicity
Low cost
What is problem with H2O as solvent?
Contains dissolved substances that could interfere with drug formulation
What must happen to H2O if solvent for manufacturing of oral solutions?
Purified
Produced by distillation, ion exchange or reverse osmosis
What co-solvents are used?
Ethanol, propylene glycol + glycerol
Why are co-solvents used?
Many drugs not H2O soluble
What do co-solvents do?
Less innocuous than water = conc within formulation low
Why does drug conc need to be below saturation solubility?
To avoid drug precipitation
What excipients are used?
Viscosity enhancers Preservatives Sweeteners Antioxidants Flavouring agents Colouring agents Other for non-oral solutions
Why are viscosity enhancers used?
Improve pourability
What are examples of viscosity enhancers?
Hydroxyethyl, cellulose, povidone, carbomer + glycerol
Why are preservatives used?
Prevent microbial growth
What are examples of preservatives?
Benzoic acid, benzalkonium chloride, sodium benzoate + glycerol
Why are sweeteners used?
Improve palatability of oral solutions
What are examples of sweeteners?
Sucrose, sorbitol + mannitol
Why are antioxidants used?
Improve stability of solutions by minimising oxidation
What are examples of antioxidants?
Ascorbic acid + sodium bisulphate
Why are flavouring agents used?
Mask unpleasant taste of drugs
What are examples of flavouring agents?
Vanilla, orange oil, menthol + liquorice
Why are colouring agents used?
Correlate with flavouring agent
What are examples of colouring agents?
Green with mint
Red with strawberry
What other excipients may be added for non-oral solutions?
Density modifiers
Isotonicity modifiers
Why must a solution remain stable?
For shelf-life
What properties of solution must remain the same for stability?
Physical Chemical Microbiological Therapeutic Toxicological
What causes solution degradation?
High temp
pH
UV light
Catalyst
What enhances solution stability?
Formulate at suitable pH
Include excipients that enhance product stability
eg. antioxidants
Packaged in containers that reduce light transmission
Purging solution with nitrogen to create nitrogen headspace
When are excipients stable?
Non toxic
Compatible with drug, containers + other excipients
Functional throughout shelf life
What does drug solubility depend on?
Molecular structure Crystal structure Particle size pKa pH of medium
What can you use to increase drug solubility?
pH modification
Co-solvents
Complexation
Surfactants + micelles
What can altering pH of medium cause?
Increase drug ionisation = increase drug solubility
What is ionisation governed by?
pH = pKa + log (base/acid)
When are WA drugs ionised?
When solvent pH increased
HA ⇌ H+ + A-
When are co-solvents used?
Used for non-ionic drugs where solubility cannot be adjusted by pH control
What do non-polar drugs dissolve in?
Non-polar solvents
Describe cyclodextrin complexation
Family of compounds made up of sugar molecules bound together in a ring 6-membered sugar ring = alpha 7-membered = beta 8-membered = gamma Hollow truncated cone shape Interior cavity hydrophobic Exterior hydrophilic
What can cyclodextrin do because of hydrophobic interior?
“Capture” hydrophobic molecules via non-covalent bonds
What can cyclodextrin do because of hydrophilic exterior?
Highly H2O soluble
What is cyclodextrin overall effect?
Increase solubility of drug
What happens with cyclodextrin oral administration?
Drug released from cyclodextrin + free drug absorbed
What do surfactants + micelles have to pass?
Hydrophilic head + hydrophobic tail
What happens to surfactants + micelles?
Accumulate at boundary between 2 phases
What do surfactants + micelles do?
Reduce surface tension of liquids
What can surfactants + micelles do to poorly H2O soluble drugs?
Solubilise in micelles to enhance drug solubility
