Lecture 18, 19 & 20: Taste Masking, Quick Oral relief Formulations & Patches

Question 1

Why is taste masking important and which formulation is hard to mask?

Answer 1

• Many drugs have bitter taste or irritate the throat.
• Affect acceptance and thus compliance
• Harder to mask in liquid formualtion -> prolonged contact in mouth

Question 2

Why is taste masking needed for paediatric formulations?

Answer 2

• Children need different dose of API and volume of liquids. More side effects
• Inability to take some dosage forms
• More sensitive to bad taste

Question 3

What are the different classes for the paediatric population?

Answer 3

• Preterm newborn infants
• Term newborn (0-28 days)
• Infants and toddlers (28days-2yrs)
• Children (2-11yrs)
• Adolescents (12-18yrs)

Question 4

What is the extrusion reflex?

Answer 4

• 5-6 months
• Solid in child, poke tongue out and push solid out. Avoid swallowing solid

Question 5

At what age can semi solids be taken?

Answer 5

• 5-6 months
• Multi particulates (powders, granules, pellets, mini tablets) can be taken by sprinking on food
• At 6 years + considered capable of swallowing conventional tablets/ capsules

Question 6

Why is liquid formulations better for children?

Answer 6

• Unable to swallow capsules or tablets
• Can tailor dose better using oral syringe

Question 7

What are the the disadvantages of liquid formulations?

Answer 7

• Taste and smell of drugs are more difficult to mask
• Generally, more expensive with limited shelf life
• Usually requires more excipients (as compared to oral solids) - must be considered with great care

Question 8

How should excipients be in paediatric populations and which are to avoid?

Answer 8

• Should be pharmacologically inactive
• Can cause adverse effects -> cant metabolise or eliminate excipients
• Benzyl alcohol, ethanol - neurotoxicity and metabolic acidosis in kids
• Polysorbate 20 & 80 - liver and kidney failure

Question 9

What does palatability mean?

Answer 9

• Overall appreciation of a medicine towards its smell, taste, texture and aftertaste
• Appearance contributes to acceptability
• Should be satisfactiory without mixing with others

Question 10

When do children develop taste buds and what parts of the tongue can you taste sweet, salty and bitter?

Answer 10

• Around 7-8th week of gestation. Structurally mature at 13-15 weeks
• Sweet - front of tongue (tip), Salty - front and sides of frony, Bitter - back middle

Question 11

What are the 3 main approaches of taste masking?

Answer 11

• Create a barrier between taste receptors and drug (coating)
• Make chemical or solubility modifications (controlling pH, esters of drug) - breaks down in body
• Overcome unpleasant taste by adding flavours or sweetners

Question 12

What is the coating technique?

Answer 12

• Coating acts as a physical barrier to the drug particles, thereby minimising interaction between drug and taste buds
• Either coat drug particle or compact into tablet then coat
• Ideally, polymers selected should prevent API release in oral cavity - while allowing intended release

Question 13

What is the adding sweetners technique in taste masking?

Answer 13

• Simplest technique can recognise from early age and like higher levels (however can have bitter taste)
• Highly water soluble, will dissolve in saliva and coat taste buds
• Sucrose is most commonly used sweetner - readily hydrolysed in intestine to absorbable fructose and glucose, can cause dental caries

Question 14

What is the alternative of adding sweetners?

Answer 14

• Sugar free sweetners
• Products that dont contain fructose, glucose or sucrose - sugar free
• Contain hydrogenated glucose syrup (lycasin), maltitol, sorbitol or xylitol - sugar free

Question 16

What are complexation techniques (Chemical or solubility modifications)?

Answer 16

• Either decreases the amount of drug particles directly exposed to taste buds or decreases oral solubility
• Beta cyclodextrin. Sweet, non-toxic, cyclic oligosaccharide
• Ring has hollow space - drug sit inside and shield from taste buds. When in body it can release - can increase solubility

Question 17

What is the taste masking pro drug technique?

Answer 17

• Prodrugs are molecules that are initially inactive but upon administration is converted to active form
• Pro-moeity (inactive group bound to drug by temp linkage). This changes chem structure and taste of drug
• When in body it breaks down by pH/enzyme and active drug released
• Pro moeity shoudnt be toxic and excreted from body

Question 18

Why are colouring agents used and why shouldnt they be used?

Answer 18

• Generally kids like brightly coloured preparations
• However, should be avoided unless necessary as associated w/ hypersensitivity and adverse reactions
• Azo-dyes = unacceptable

Question 20

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What are some attributes of liquid formulations and solid formulations?

Answer 20

• Liquid: Viscosity (pourability/thickness), smoothness, slipperiness, mouthcoating
• Solid: Roughness, Hardness, Fracturability (force in which breaks), Cohesiveness, Tootpacking (sticks on teeth)

Question 21

What are some excipients used for sensory attributes?

Answer 21

• Propylene glycol: sweet/bitter (in high conc), oily and warming
• Glycerin: Sweet

Question 22

What are the requirements of acute pain relief medications?

Answer 22

• Rapid onset within mins (tablets take hours)
• Rapid drug dissolution
• Rapid drug absorption
• Minimal effort to take

Question 23

What are the disadvantages of oral medicines?

Answer 23

• Long transit time through GI tract: long distance to blood circulation, slow onset
• First pass effects: GI degradation, first pass hepatic metabolism. Reduce bioavalability
• Difficulty swallowing

Question 24

What are the 3 different oral quick relief formulations?

Answer 24

• Oromucosal Absorption: Sublingual (under tongue), Buccal (inside cheek)
• Dispersible: Disperse in water then drink
• Orodispersible: Dissolve in saliva then swallow

Question 25

What are the advantages of Sublingual and buccal formulations?

Answer 25

• Rapid onset
• No swallowing
• Mild oromucosal environment avoids drug degradation
• No first pass metabolism -> good bioavailability

Question 26

What are the disadvantages of sublingual and buccal formulations?

Answer 26

• Potential unpleasant taste
• Salivary washout (drug needs to stay to get absorbed)
• Interferes w/ eating and drinking

Question 27

What are the advantages of dispersible formulations?

Answer 27

• Rapid onset - dissolution outside of body
• Taken as a liquid, mitigating issues w/ swallowing and choking
• Improved bioavailability

Question 28

What are the disadvanatges of Dispersible formulations?

Answer 28

• Potential unpleasant taste
• Potable water requirement

Question 29

What are the advantages of orodispersible formulations?

Answer 29

• Rapid onset
• Overcomes issues w/ swallowing and choking
• No potable water requirement
• Improved bioavalability

Question 30

What are the disadvantages of orodispersible formulations?

Answer 30

• Potential unpleasant taste

Question 31

What are formulation considerations for oral quick relief formulations?

Answer 31

• Rapid dissolution required: Superdisintegrant or effervescent disintegrant
• Flavouring/ Sweetner - cant use coating (needs to be in contact w/ taste buds)
• Moisture Sensitive - cause they dissolve in water readily

Question 32

What are the different layers of the oro mucosa and what layer does it need to reach to get absorbed?

Answer 32

• Main keratinised barrier (oral epithelium)
• Basement Membrane + Lamina Propia
• Sub mucosa (contains blood vessels) - needs to reach to be dissolved

Question 33

Where are each of the salivary glands (Parotid, Sublingual, Submandibular) located?

Answer 33

• Parotid: Cheek
• Sublingual: Each side below tongue, on the floor of mouth
• Submandibular: both sides, just under and deep to the jaw, towards the back of the mouth

Question 34

How does the drug from the mouth enter bloodstream?

Answer 34

• Sublingual and Lingual Veins: The sublingual and lingual mucosa have a rich supply of capillaries and veins.
• Drainage to the Internal Jugular Vein: Carries blood from head & neck to the heart.
• Direct Entry into Systemic Circulation: flows into the superior vena cava, which leads directly to the heart. The heart then body.