Routes of Administration - oral solutions Flashcards
Define pharmaceutical solutions.
Liquid preparations in which the therapeutic agent and excipients are dissolved in a liquid solvent system
How are the drugs present in oral solutions.
The drug is present as molecules or ions throughout the solvent - needs to be fully solubilised in the solution
What are the advantages of oral solutions?
- fast onset of action
- dose uniformity is assured
- volume of liquid dose can be measured accurately to tailor doses
- easy to swallow
- easy to manufacture
What are the disadvantages of oral solutions?
- Less stable than solid dosage forms
- Many drugs are poorly soluble in water
- Unpleasant taste and odours are difficult to mask
- Packaging costs, transportation and storage
What are the major signs of instability?
- Colour change
- Precipitation
- Microbial growth
State the properties of oral solutions.
- Must be stable
- Palatable: flavouring, colouring and sweetening agents added
- Appropriate viscosity for palatability and pour ability
- Dose in multiples of 5 ml for convenience
- At physiological pH where possible
- Drug concentration needs to well below saturation solubility to avoid drug precipitation
Why is water the most commonly used solvent?
- Lack of toxicity
- Low cost
- However tap water contains dissolved substances that could interfere with the drug formulation
How is purified water manufactured?
By distillation, ion exchange, or reverse osmosis
State the function of viscosity enhancers.
- Improves pouring quality
- e.g. glycerol
State the function of preservatives.
- Prevent microbial growth
e.g. benzoic acid
State the function of sweeteners.
- Improve palatability of oral solutions
e.g. sucrose
State the function of antioxidants.
- Improve stability of the solutions by minimising oxidation
e.g. ascorbic acid
State the function flavouring agents
- Mask unpleasant taste of drugs
e.g. vanilla
State the function of colouring agents.
- Correlate with the flavouring agent
e.g. green with mint
Which properties must remain the same for the duration of the solution shelf life?
– Physical (e.g. colour, viscosity, odour, taste, clarity).
– Chemical (e.g. within limits for API, total impurities).
– Microbiological (e.g. resistant to microbial growth).
– Therapeutic (e.g. maintain efficacy).
– Toxicological (e.g. no significant increase in toxicity).
State the factors affecting chemical degradation.
- High temp
- pH
- Oxygen
- UV light
- Catalysis
State the ways to enhance solution stability.
- Formulate at a suitable pH.
- Include excipients to enhance product stability.
- Include antioxidants or metal chelators to reduce oxidation.
- Packaged in containers that reduce light transmission.
- Purging solution with nitrogen to create nitrogen
headspace.
What is the reason for the enhancement of drug solubility?
Achieve desired dose and effect/BA
Avoid drug precipitation
What does drug aqueous solubility depend on?
Molecular and crystal structure
solvent
pKa
pH of the medium
How can the solubility of a drug be increased?
pH modification
Co-solvents
Complexation
Surfactants
What are most drugs? (pH)
Either weak acids or weak bases
What is ionisation governed by?
by pKa and the Henderson-Hasselbalch equations
pH = pKa + log [A-]/[HA]
What does altering pH of the medium lead to?
- Can increase drug ionisation - which increases drug solubility
How is the final solvent pH chosen?
- With a balance between drug solubility and formulation stability
Describe the protonated form of a weak acid.
Non-ionised
Describe the protonated form of a weak base.
Ionised
What is a co-solvent system?
- One in which a water miscible or partially miscible organic solvent is mixed with water to form a modified aqueous solution
- The phenomenon is called cosolvency
What is the reason for cosolvents?
- Many drugs are not water-soluble.
- Mostly used for non-ionic drugs where solubility cannot be adjusted by
pH control. - ‘Like dissolves like’ principle.
- Non-polar drugs generally dissolve in non-polar solvents, i.e. poorly soluble in water. Reducing the polarity of the solvent can
increase solubility.
What are cyclodextrins?
A family of compounds made up of sugar molecules bound together in a ring
What is the overall effect of cyclodextrins?
- To increase aqueous solubility of drug
- Upon oral administration drug is released from cyclodextrins and the free drug can be absorbed
What are the two regions of surfactants?
- Hydrophobis
- Hydrophilic
What is the function of surfactants?
- Reduces the surface tensions of liquids
- Self-assemble to form micelles at the critical micelle concentration
How can poorly water soluble drugs be enhanced?
- They can be solubilised in micelles to enhance drug solubility
What are some considerations when switching between oral formulations of the same drug.
- Administration times
- Bioavailability differences
- Excipients (allergy)
- Modified release formulations
- Site of action
- Narrow therapeutic index, medicines
- Some formulations are not interchangeable
Which medicines require extra care when switching between liquid and tablet/capsule formulations?
- Carbamazepine
- Citalopram
- Digoxin
