Routes of Administration - oral solutions

Question 1

Define pharmaceutical solutions.

Answer 1

Liquid preparations in which the therapeutic agent and excipients are dissolved in a liquid solvent system

Question 2

How are the drugs present in oral solutions.

Answer 2

The drug is present as molecules or ions throughout the solvent - needs to be fully solubilised in the solution

Question 3

What are the advantages of oral solutions?

Answer 3

• 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

Question 4

What are the disadvantages of oral solutions?

Answer 4

• 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

Question 5

What are the major signs of instability?

Answer 5

• Colour change
• Precipitation
• Microbial growth

Question 6

State the properties of oral solutions.

Answer 6

• 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

Question 7

Why is water the most commonly used solvent?

Answer 7

• Lack of toxicity
• Low cost
• However tap water contains dissolved substances that could interfere with the drug formulation

Question 8

How is purified water manufactured?

Answer 8

By distillation, ion exchange, or reverse osmosis

Question 9

State the function of viscosity enhancers.

Answer 9

• Improves pouring quality
• e.g. glycerol

Question 10

State the function of preservatives.

Answer 10

• Prevent microbial growth
  e.g. benzoic acid

Question 11

State the function of sweeteners.

Answer 11

• Improve palatability of oral solutions
  e.g. sucrose

Question 12

State the function of antioxidants.

Answer 12

• Improve stability of the solutions by minimising oxidation
  e.g. ascorbic acid

Question 13

State the function flavouring agents

Answer 13

• Mask unpleasant taste of drugs
  e.g. vanilla

Question 14

State the function of colouring agents.

Answer 14

• Correlate with the flavouring agent
  e.g. green with mint

Question 15

Which properties must remain the same for the duration of the solution shelf life?

Answer 15

– 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).

Question 16

State the factors affecting chemical degradation.

Answer 16

• High temp
• pH
• Oxygen
• UV light
• Catalysis

Question 17

State the ways to enhance solution stability.

Answer 17

• 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.

Question 18

What is the reason for the enhancement of drug solubility?

Answer 18

Achieve desired dose and effect/BA
Avoid drug precipitation

Question 19

What does drug aqueous solubility depend on?

Answer 19

Molecular and crystal structure
solvent
pKa
pH of the medium

Question 20

How can the solubility of a drug be increased?

Answer 20

pH modification
Co-solvents
Complexation
Surfactants

Question 21

What are most drugs? (pH)

Answer 21

Either weak acids or weak bases

Question 22

What is ionisation governed by?

Answer 22

by pKa and the Henderson-Hasselbalch equations
pH = pKa + log [A-]/[HA]

Question 23

What does altering pH of the medium lead to?

Answer 23

• Can increase drug ionisation - which increases drug solubility

Question 24

How is the final solvent pH chosen?

Answer 24

• With a balance between drug solubility and formulation stability

Question 25

Describe the protonated form of a weak acid.

Answer 25

Non-ionised

Question 26

Describe the protonated form of a weak base.

Answer 26

Ionised

Question 27

What is a co-solvent system?

Answer 27

• 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

Question 28

What is the reason for cosolvents?

Answer 28

• 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.

Question 29

What are cyclodextrins?

Answer 29

A family of compounds made up of sugar molecules bound together in a ring

Question 30

What is the overall effect of cyclodextrins?

Answer 30

• To increase aqueous solubility of drug
• Upon oral administration drug is released from cyclodextrins and the free drug can be absorbed

Question 31

What are the two regions of surfactants?

Answer 31

• Hydrophobis
• Hydrophilic

Question 32

What is the function of surfactants?

Answer 32

• Reduces the surface tensions of liquids
• Self-assemble to form micelles at the critical micelle concentration

Question 33

How can poorly water soluble drugs be enhanced?

Answer 33

• They can be solubilised in micelles to enhance drug solubility

Question 34

What are some considerations when switching between oral formulations of the same drug.

Answer 34

• Administration times
• Bioavailability differences
• Excipients (allergy)
• Modified release formulations
• Site of action
• Narrow therapeutic index, medicines
• Some formulations are not interchangeable

Question 35

Which medicines require extra care when switching between liquid and tablet/capsule formulations?

Answer 35

• Carbamazepine
• Citalopram
• Digoxin