Oral Solutions

Question 1

What is a solution?

Answer 1

A mixture of two or more components that form single homogenous phase at molecular level

Question 2

What is a solute?

Answer 2

Components dispersed as molecules or ions in solvent

Question 3

What is a solvent?

Answer 3

Liquid capable to dissolve a substance + usually major component in a solution + determine phase of system

Question 4

Is a solution optically clear?

Answer 4

YES

Question 5

What are the advantages of solutions?

Answer 5

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

Question 6

What are the disadvantages of solutions?

Answer 6

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

Question 7

What are the oral solution properties?

Answer 7

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

Question 8

What is the most solvent?

Answer 8

H2O

Question 9

Why is H2O most common solvent?

Answer 9

Lack of toxicity

Low cost

Question 10

What is problem with H2O as solvent?

Answer 10

Contains dissolved substances that could interfere with drug formulation

Question 11

What must happen to H2O if solvent for manufacturing of oral solutions?

Answer 11

Purified

Produced by distillation, ion exchange or reverse osmosis

Question 12

What co-solvents are used?

Answer 12

Ethanol, propylene glycol + glycerol

Question 13

Why are co-solvents used?

Answer 13

Many drugs not H2O soluble

Question 14

What do co-solvents do?

Answer 14

Less innocuous than water = conc within formulation low

Question 15

Why does drug conc need to be below saturation solubility?

Answer 15

To avoid drug precipitation

Question 16

What excipients are used?

Answer 16

Viscosity enhancers
Preservatives
Sweeteners
Antioxidants
Flavouring agents
Colouring agents 
Other for non-oral solutions

Question 17

Why are viscosity enhancers used?

Answer 17

Improve pourability

Question 18

What are examples of viscosity enhancers?

Answer 18

Hydroxyethyl, cellulose, povidone, carbomer + glycerol

Question 19

Why are preservatives used?

Answer 19

Prevent microbial growth

Question 20

What are examples of preservatives?

Answer 20

Benzoic acid, benzalkonium chloride, sodium benzoate + glycerol

Question 21

Why are sweeteners used?

Answer 21

Improve palatability of oral solutions

Question 22

What are examples of sweeteners?

Answer 22

Sucrose, sorbitol + mannitol

Question 23

Why are antioxidants used?

Answer 23

Improve stability of solutions by minimising oxidation

Question 24

What are examples of antioxidants?

Answer 24

Ascorbic acid + sodium bisulphate

Question 25

Why are flavouring agents used?

Answer 25

Mask unpleasant taste of drugs

Question 26

What are examples of flavouring agents?

Answer 26

Vanilla, orange oil, menthol + liquorice

Question 27

Why are colouring agents used?

Answer 27

Correlate with flavouring agent

Question 28

What are examples of colouring agents?

Answer 28

Green with mint | Red with strawberry

Question 29

What other excipients may be added for non-oral solutions?

Answer 29

Density modifiers | Isotonicity modifiers

Question 30

Why must a solution remain stable?

Answer 30

For shelf-life

Question 31

What properties of solution must remain the same for stability?

Answer 31

``` Physical Chemical Microbiological Therapeutic Toxicological ```

Question 32

What causes solution degradation?

Answer 32

High temp pH UV light Catalyst

Question 33

What enhances solution stability?

Answer 33

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

Question 34

When are excipients stable?

Answer 34

Non toxic Compatible with drug, containers + other excipients Functional throughout shelf life

Question 35

What does drug solubility depend on?

Answer 35

``` Molecular structure Crystal structure Particle size pKa pH of medium ```

Question 36

What can you use to increase drug solubility?

Answer 36

pH modification Co-solvents Complexation Surfactants + micelles

Question 37

What can altering pH of medium cause?

Answer 37

Increase drug ionisation = increase drug solubility

Question 38

What is ionisation governed by?

Answer 38

pH = pKa + log (base/acid)

Question 39

When are WA drugs ionised?

Answer 39

When solvent pH increased | HA ⇌ H+ + A-

Question 40

When are co-solvents used?

Answer 40

Used for non-ionic drugs where solubility cannot be adjusted by pH control

Question 41

What do non-polar drugs dissolve in?

Answer 41

Non-polar solvents

Question 42

Describe cyclodextrin complexation

Answer 42

``` 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 ```

Question 43

What can cyclodextrin do because of hydrophobic interior?

Answer 43

"Capture" hydrophobic molecules via non-covalent bonds

Question 44

What can cyclodextrin do because of hydrophilic exterior?

Answer 44

Highly H2O soluble

Question 45

What is cyclodextrin overall effect?

Answer 45

Increase solubility of drug

Question 46

What happens with cyclodextrin oral administration?

Answer 46

Drug released from cyclodextrin + free drug absorbed

Question 47

What do surfactants + micelles have to pass?

Answer 47

Hydrophilic head + hydrophobic tail

Question 48

What happens to surfactants + micelles?

Answer 48

Accumulate at boundary between 2 phases

Question 49

What do surfactants + micelles do?

Answer 49

Reduce surface tension of liquids

Question 50

What can surfactants + micelles do to poorly H2O soluble drugs?

Answer 50

Solubilise in micelles to enhance drug solubility