D5- medicine design and manufacturing (liquid medicines)

Question 1

what are the different types of liquid medicine

Answer 1

-solution
-suspension
-emulsion

Question 2

Describe solution medicine

Answer 2

All ingredients are dissolved and
therefore present as single molecules
within the liquid

Question 3

Describe suspension medicines

Answer 3

Insoluble solid particles dispersed in the liquid

Question 4

Describe emulsion medicine

Answer 4

Insoluble liquid droplets dispersed in
another liquid

Question 5

What are the common excipients in liquid medicines

Answer 5

1.Vehicles
2. Preservatives
3. Antioxidants
4. Buffers
5. Sweeteners
6. Flavours
7. Colours
8. Solubility enhancers
9. Thickening agents
10. Emulsifying agents

Question 6

which excipients are stabilisers

Answer 6

preservatives, antioxidants, buffers

Question 7

which excipients make liquid medicine more appealing

Answer 7

sweeteners, flavours, colours

Question 8

are excipients used as additives in food?

Answer 8

yes, sometimes identified by their E number. It is all approved and safe but some patients may react too them

Question 9

what is the vehicle of a liquid medicine? and what is most common

Answer 9

the main liquid ingredient. most common is water

Question 10

Describe what the water needed for liquid medicine

Answer 10

• Purified Water BP (low level of salts and impurities)
• Water for Injection BP (sterile and particle-free)

Question 11

what thick sweet liquids are used as a vehicle?

Answer 11

syrup, sorbitol solution, glycerol
* More ‘palatable’
* Easier to pour

Question 12

what other liquids are used as a vehicle

Answer 12

alcohol, ether, propylene glycol
* Mainly for external medicines (ex: wart remover, acne treatment, ear drops)

Question 13

what are stabilisers used in liqiud medicines

Answer 13

preservatives, antioxidants, chelating agents, buffers

Question 14

why are preservatives added

Answer 14

• Inhibit the growth of microorganisms
• Added to medicines containing water to prevent
• Food poisoning (oral liquids)
• Contamination of the medicine and re-infection of the patient (ex: eye drops)
• Microorganisms degrading the medicine

Question 15

what are the issues with preservatives

Answer 15

-many patients react to them so pharmacist must select appropriate product or create ‘special’ manufactured without preservative

Question 16

what other ingredients can act as preservatives

Answer 16

• Glycerol, sorbitol, syrup but only at a high concentration
• Alcohol > 10% (volatile so short self life)
• Chloroform (diluted) (volatile)

Question 17

Describe the antioxidants stabilisers

Answer 17

• React with dissolved oxygen
• are oxidised more easily than the drug or other excipients
• terminate oxidation/free radical reactions

Question 18

Describe chelating agents, stabilisers

Answer 18

• Form complexes with heavy metal ions
  → Reduce their ability to catalyse oxidation reactions
• Example: EDTA (look at one note for structure)

Question 19

why is EDTA infusion used

Answer 19

to remove excess calcium (Ca2+) from the blood of patients with bone cancer

Question 20

Describe the buffer stabilisers

Answer 20

control pH of medicine

Question 21

why are buffers important to control pH

Answer 21

-Drug and excipients may only be soluble in a specific pH range
-To prevent drug/excipients degrading
-Avoid pain/stinging (ex: eye or nasal drops)
-Avoid protein denaturation, cell death, tissue damage, etc…
-taste

Question 22

how do buffers work

Answer 22

-mixture of weak acid and its salt or weak base and its salt
(look on one note)
-They are most effective at pH values ± 1 of their pKa

Question 23

What are the common buffers and their pH range

Answer 23

Acetate 3.5-5.5
Citrate 3.0-6.2
Phosphate 5.8-8.0
Trisaminomethane (TRIS or THAM) 7-9

Question 24

what kind of sweeteners are used

Answer 24

Sugars (sucrose, glucose,
lactose, fructose), Glycerol, Sugar alcohols (sorbitol, maltitol,
xylitol, mannitol), Artificial sweeteners
(saccharin, aspartame)

Question 25

Describe sugars used as sweeteners

Answer 25

Syrup BP (67% of sucrose in water) * Causes tooth decay (‘cariogenic’) * Preservative if undiluted

Question 26

Describe glycerol used as sweetener

Answer 26

Glycerol BP Often used in cough medicines (‘demulcent’)

Question 27

Describe sugar alcohols used as sweetener

Answer 27

Sorbitol BP (70% sorbitol in water) * Often used in ‘sugar-free’ medicines * No tooth decay and suitable for diabetics * Not ‘calorie-free’! * Can cause bloating, cramps, diarrhoea

Question 28

Describe artificial sweeteners as sweetener

Answer 28

* Different taste * No calories or tooth decay * Safety?

Question 29

Describe flavouring

Answer 29

* To ‘taste mask’ the drugs * Can be natural, natural identical or artificial (table on one note about flavourings)

Question 30

What are the traditional flavourings?

Answer 30

oils, spirits and tinctures, concentrated waters, water, syrups

Question 31

Describe oils used as traditional flavourings

Answer 31

The pure oil. Very concentrated ex: peppermint oil

Question 32

Describe spirits and tinctures used as traditional flavourings

Answer 32

Concentrated oil or flavour in alcohol ex: peppermint spirit

Question 33

Describe concentrated waters used in traditional flavourings

Answer 33

Concentrated solution or emulsion in water ex: concentrated peppermint water,concentrated chloroform water

Question 34

Describe waters used in traditional flavourings

Answer 34

The most diluted form ex: double strength chloroform water

Question 35

Describe syrups used in traditional medicines

Answer 35

A flavour syrup ex: Orange syrup BP

Question 36

Describe colours used in liquid medicines

Answer 36

-synthetic colour: Commonly have an azo group –N=N, A few safe to ingest, more permitted for skin use, cosmetics, clothing etc -inorganic colurs: Iron oxides (yellow, red, black) in tablet coats Titanium dioxide (white) - ‘opacifiant’ -natural : look on one note

Question 37

what are the issues with colours

Answer 37

-not essential -adverse effects of synthetic colours -natural colourings are usually safer but less chemically stable and can cause food allergy

Question 38

Describe solubility enhancers in liquid medicines

Answer 38

* Help solubilising the drug (and excipients) * Common examples: cosolvents (Contains 19% alcohol) and surfactants (Form micelles in water, Help dissolving hydrophobic drugs)

Question 39

what is the issue with suspensions

Answer 39

Poor physical stability, prone to separation and ‘caking’ (when particles bound together)- there can be areas of low drug content (ineffective) and areas of high drug content (overdose)

Question 40

how do you prevent separation and caking?

Answer 40

-shake the medicine snd tell patient -decrease the size of suspended particles (grinding/ sieving) -Increase the viscosity of the vehicle (Add a suspending agent/thickening agent) -Flocculate (Adjust surface charge) -Improve the ‘wetting’ of the suspended particles (Add a surfactant)

Question 41

Describe thickening agents added to liquid medicines

Answer 41

* Increase the viscosity of the vehicle to slow down the fall of the suspended particles * Can also be used to increase the residence time of external medicines at the site of action

Question 42

what are common examples of thickening agents?

Answer 42

cellulose ethers, polysaccharides, synthetic polymers, proteins

Question 43

how to formulate a suspension?

Answer 43

* Design the medicine to be buffered below pH 4 * Use fruit flavours & colours to match the acid pH. * Use aniseed/liquorice to mask aftertaste. * You can use benzoates as preservatives as pH2-5 * You cannot use alginates as thickeners.