WEEK 3 - Taste Masking Paediatric Formulations Flashcards
Tatse Background
Including info on: taste buds, tatse receptors, 5 tastant types
- Tatse is developed before birth + continues to mature postnatally
- Infants within hrs of birth reject bitter tastes and prefer sweet tatstes
- sensitivity to salt develops around 4 months
TASTE BUDS:
- IS entire structure inc. receptor, microvilli
- have 2000-10000 (↓ with age)
- have a life span of 10 days
- have ↓ replacement rate with age
- each bud can sense all 5 tastants BUT some buds can sense one more than the other
TASTE RECEPTORS
- found on neuroepithelial cells
- Ion channel receptors = sour and salty
- G portien-coupled receptors = sweet, bitter and umami
- sweet tasting formulations reduce pain in children due to stimulating release of endorphins
TASTANT TYPES
1. Sour - acidic
2. Salty - helps electrolytic balance
3. Sweet - identifies highly energetic nutrients
4. Bitter - associated with harmful / toxic substances
5. Umami / savoury - due to glutumate
List all factors affecting taste perception in children
- Platability
- Odours
- Irritation
- Flavour
How does “platability” affect taste perception in children
Platability - the overall quality / acceptance of the medicine
- taste, smell, aftertaste, texture, mouthfeel, appearance ALL affect this
How does “odours” affect taste perception in children
Odour stimule recahes olfactory receptor in 2 ways:
1. Orthonasal Route = direct inhalation through nose
- most common route
- Retronasal Route = ododurs that reach nose from throat when eating
- occurs at back or oral cavity near roof of nasal pharynx
SOLUTIONS:
- Plug child’s nose to prevent smelling odour (may still taste bitter)
- Mask bitterness by flavouring medicine with pleasant odours
How does “irritation” affect taste perception in children
Irritation - sensations like pain, heat, tingling, coolneess, burning, itching
- chemical stimulates receptors + free nerve endings on the trigeminal or vagus nerve
Examples:
- Methol interacts with channels sensitive to cooling
- Chilli contain capsacin stimualtes receptors causing burning
- ibuprofen (liquid) irritates throat causing itch, tickle, cough
How does “flavour” affect taste perception in children
- Natural flavours are preffered as they offer better taste and platability
- Artificial flavours are easier to characterise + chemically stable
- May use a combination of flavours to improve APIs taste profile
- Acidic APIs = use citrus and berry
- Alkaline APIs = use banana, caramel, cherry
Explain the structure of the olfactory epithelium
- Epithelium has 6-10 million receptor cells detecting chemicals G-protein receptors on cilia = detect tastants
- Have a large surface area (SA) due to long extending cilia
- Found in olfactory bulb
What are common paediatric oral dosage forms
Oral Liquids
- Syrup
- Solution
- Suspension
NOTE:
- Cut off for liquid use is 6-8 years
- Prefered pH 5.5 to 7.5
<5.5 = degrade tooth enamel
>8 = unpleasant taste + hard to preserve
Oral Solids:
- Soluble Films
- Orally Disintegrating Tablets
- Soluble Tablets
- Chewable Tablets
- Minitablets
List all taste masking strategies for different APIs
APIs (active pharmaceutical ingredients)
- Sensory Approach
- Solubility Approach
- Barrier Approach
- Complexation Approach
- Chemical Approach
Explain how “Sensory Approach” is used as a taste masking strategy
APIs (active pharmaceutical ingredients)
Includes use of flavouring agents, sweeteners, amino acids and sodium salts
- The SIMPLEST approach
- not good for very bitter or highly water-soluble drugs - Used with OTHER APPROACHES to IMPROVE EFFICENCY
NATURAL SWEETNERS
- Add texture + body to product
- e.g. sugar alcohols (mannitol, glycerol, sorbitol)
- e.g. dextrose, sucrose
- Prefer natural sweetners
- Sucrose issues inc. may affect diabetics, dental issues (dissolve tooth enamel), intolerance
- Sugar alcohols have no effect on blood glucose, no carciogenic effect, reduced calories BUT GI issues
ARTIFICIAL SWEETNERS
- Add intense sweet taste
- e.g. sodium saccharin, sucralose, aspartame, acesulfame potassium
- Aspartame (200x sweeter than sucrose),
- large amounts are neurotoxic = seziures
SODIUM SALTS (a cation)
- Mask / reduce bitter tatses
- Can also intensify sweetness of a liquid (by blocking bitterness)
- concerns of consuming excess salts in children
NOTE:
- May use COMBINATION of SWEETNERS to mask unpleasant taste
Explain how “Solubility Approach” is used as a taste masking strategy
APIs (active pharmaceutical ingredients)
Solubility varies with pH
- can ↑ solubility by changing pH, granulation
- can ↓ solubility by adding alkalising or acidifying agent
- Keep the API unionised
- ↓ rate of dissolution in saliva
- limit solubility of compound in fomrulation vehicle
Explain how “Barrier Approach” is used as a taste masking strategy
APIs (active pharmaceutical ingredients)
Includes use of: Viscosity modifier, Coating (tablet, granules, micro- and nano-capsules)
POLYMER FILM-COATING
- Use of protective layer around drug particle to prevent / ↓ exposure of drug to taste perception
- a physical barrier between drug and taste buds on tongue
- SIMPLE approach = COMMONLY used
- can include coating, granulation, microencapsulation
- Coating acts as an insolbule barrier at pH of saliva (6-7)
- Coating dissolves after passing through mouth
LIPID COATING
- Use of mono/di/triglycerides or waxes
- Alternative to polymer coating
- Suitable for moisture sensitive APIs
- Amount of excipient required is less compared to polymers
- Do NOT crack during compression into tablets
- Inexpensive comapred to polymer coating
- COMMON USE: controlled drug delivery, sustained release and taste masking
VISCOSITY MODIFIER
(i.e. thickening agents)
- ↑ viscosity = ↓ settling rate of molecules (as it is a suspending agent)
- e.g. gums, carbohydrates
High viscosity:
- prevents drug coming into direct contact with taste buds
- improves pourability (flow of liquid from bottle)
Explain how “Complexation Approach” is used as a taste masking strategy
APIs (active pharmaceutical ingredients)
Includes use of: Ion exchange resins, Cyclodextrin
ION EXCHANGE RESINS (IER)
- Resins are insoluble in the body at ANY pH
- IER create weak ionic bonds with oppositely charged ionised drug forming insoluble adsorbates / resinates
- these insoluble forms prevent drug-resin complex from dissociating under saliva pH (6-7) = drug isnt released in mouth
- maintains druv stability
- Masks taste and odour of drug
- When drug reaches stomach drug is released (bioavailable), as there is a ↑ conc. of ions in stomach which will displace drug
CYCLODEXTRINS
- Have a hydrophillic outer surface + hydrophobic inner cavity
- Protects drug from direct contact with taste bud
- Can be obtained from starch
- Cyclodextrin molecule is degraded in gut by enzymes releaseing the drug from the complex
- Expensive, not commonly used
Explain how “Chemical Approach” is used as a taste masking strategy
APIs (active pharmaceutical ingredients)
Includes use of: Prodrugs
- Prodrug = inert compound that releases active drug after biotransformation
- Improve buccal delivery, mask taste
- Less solubility of drug
What medicines should have child resistant packaging
Medicines containing:
- Aspirin
- Paracetamol
- packaging can not be any colour but WHITE if for children ≤12 and solid form
- >24mg of elemental iron
DON’T NEED PACKAGING IF:
- effervescent
- single dose unit
