D5- medicine design and manufacturing (liquid medicines) Flashcards
what are the different types of liquid medicine
-solution
-suspension
-emulsion
Describe solution medicine
All ingredients are dissolved and
therefore present as single molecules
within the liquid
Describe suspension medicines
Insoluble solid particles dispersed in the liquid
Describe emulsion medicine
Insoluble liquid droplets dispersed in
another liquid
What are the common excipients in liquid medicines
1.Vehicles
2. Preservatives
3. Antioxidants
4. Buffers
5. Sweeteners
6. Flavours
7. Colours
8. Solubility enhancers
9. Thickening agents
10. Emulsifying agents
which excipients are stabilisers
preservatives, antioxidants, buffers
which excipients make liquid medicine more appealing
sweeteners, flavours, colours
are excipients used as additives in food?
yes, sometimes identified by their E number. It is all approved and safe but some patients may react too them
what is the vehicle of a liquid medicine? and what is most common
the main liquid ingredient. most common is water
Describe what the water needed for liquid medicine
- Purified Water BP (low level of salts and impurities)
- Water for Injection BP (sterile and particle-free)
what thick sweet liquids are used as a vehicle?
syrup, sorbitol solution, glycerol
* More ‘palatable’
* Easier to pour
what other liquids are used as a vehicle
alcohol, ether, propylene glycol
* Mainly for external medicines (ex: wart remover, acne treatment, ear drops)
what are stabilisers used in liqiud medicines
preservatives, antioxidants, chelating agents, buffers
why are preservatives added
- 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
what are the issues with preservatives
-many patients react to them so pharmacist must select appropriate product or create ‘special’ manufactured without preservative
what other ingredients can act as preservatives
- Glycerol, sorbitol, syrup but only at a high concentration
- Alcohol > 10% (volatile so short self life)
- Chloroform (diluted) (volatile)
Describe the antioxidants stabilisers
- React with dissolved oxygen
- are oxidised more easily than the drug or other excipients
- terminate oxidation/free radical reactions
Describe chelating agents, stabilisers
- Form complexes with heavy metal ions
→ Reduce their ability to catalyse oxidation reactions - Example: EDTA (look at one note for structure)
why is EDTA infusion used
to remove excess calcium (Ca2+) from the blood of patients with bone cancer
Describe the buffer stabilisers
control pH of medicine
why are buffers important to control pH
-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
how do buffers work
-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
What are the common buffers and their pH range
Acetate 3.5-5.5
Citrate 3.0-6.2
Phosphate 5.8-8.0
Trisaminomethane (TRIS or THAM) 7-9
what kind of sweeteners are used
Sugars (sucrose, glucose,
lactose, fructose), Glycerol, Sugar alcohols (sorbitol, maltitol,
xylitol, mannitol), Artificial sweeteners
(saccharin, aspartame)
Describe sugars used as sweeteners
Syrup BP (67% of sucrose in water)
* Causes tooth decay (‘cariogenic’)
* Preservative if undiluted
Describe glycerol used as sweetener
Glycerol BP
Often used in cough medicines (‘demulcent’)
Describe sugar alcohols used as sweetener
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
Describe artificial sweeteners as sweetener
- Different taste
- No calories or tooth decay
- Safety?
Describe flavouring
- To ‘taste mask’ the drugs
- Can be natural, natural identical or artificial
(table on one note about flavourings)
What are the traditional flavourings?
oils, spirits and tinctures, concentrated waters, water, syrups
Describe oils used as traditional flavourings
The pure oil. Very concentrated
ex: peppermint oil
Describe spirits and tinctures used as traditional flavourings
Concentrated oil or flavour in alcohol
ex: peppermint spirit
Describe concentrated waters used in traditional flavourings
Concentrated solution or emulsion in
water ex: concentrated peppermint water,concentrated chloroform water
Describe waters used in traditional flavourings
The most diluted form
ex: double strength chloroform water
Describe syrups used in traditional medicines
A flavour syrup
ex: Orange syrup BP
Describe colours used in liquid medicines
-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
what are the issues with colours
-not essential
-adverse effects of synthetic colours
-natural colourings are usually safer but less chemically stable and can cause food allergy
Describe solubility enhancers in liquid medicines
- Help solubilising the drug (and excipients)
- Common examples: cosolvents (Contains 19% alcohol) and surfactants (Form micelles in water,
Help dissolving hydrophobic drugs)
what is the issue with suspensions
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)
how do you prevent separation and caking?
-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)
Describe thickening agents added to liquid medicines
- 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
what are common examples of thickening agents?
cellulose ethers, polysaccharides, synthetic polymers, proteins
how to formulate a suspension?
- 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.
