Lecture 18, 19 & 20: Taste Masking, Quick Oral relief Formulations & Patches Flashcards
(55 cards)
1
Q
Why is taste masking important and which formulation is hard to mask?
A
- Many drugs have bitter taste or irritate the throat.
- Affect acceptance and thus compliance
- Harder to mask in liquid formualtion -> prolonged contact in mouth
2
Q
Why is taste masking needed for paediatric formulations?
A
- Children need different dose of API and volume of liquids. More side effects
- Inability to take some dosage forms
- More sensitive to bad taste
3
Q
What are the different classes for the paediatric population?
A
- Preterm newborn infants
- Term newborn (0-28 days)
- Infants and toddlers (28days-2yrs)
- Children (2-11yrs)
- Adolescents (12-18yrs)
4
Q
What is the extrusion reflex?
A
- 5-6 months
- Solid in child, poke tongue out and push solid out. Avoid swallowing solid
5
Q
At what age can semi solids be taken?
A
- 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
6
Q
Why is liquid formulations better for children?
A
- Unable to swallow capsules or tablets
- Can tailor dose better using oral syringe
7
Q
What are the the disadvantages of liquid formulations?
A
- 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
8
Q
How should excipients be in paediatric populations and which are to avoid?
A
- 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
9
Q
What does palatability mean?
A
- Overall appreciation of a medicine towards its smell, taste, texture and aftertaste
- Appearance contributes to acceptability
- Should be satisfactiory without mixing with others
10
Q
When do children develop taste buds and what parts of the tongue can you taste sweet, salty and bitter?
A
- 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
11
Q
What are the 3 main approaches of taste masking?
A
- 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
12
Q
What is the coating technique?
A
- 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
13
Q
What is the adding sweetners technique in taste masking?
A
- 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
14
Q
What is the alternative of adding sweetners?
A
- Sugar free sweetners
- Products that dont contain fructose, glucose or sucrose - sugar free
- Contain hydrogenated glucose syrup (lycasin), maltitol, sorbitol or xylitol - sugar free
15
Q
A
16
Q
What are complexation techniques (Chemical or solubility modifications)?
A
- 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
17
Q
What is the taste masking pro drug technique?
A
- 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
18
Q
Why are colouring agents used and why shouldnt they be used?
A
- Generally kids like brightly coloured preparations
- However, should be avoided unless necessary as associated w/ hypersensitivity and adverse reactions
- Azo-dyes = unacceptable
19
Q
A
20
Q
dnt the
What are some attributes of liquid formulations and solid formulations?
A
- Liquid: Viscosity (pourability/thickness), smoothness, slipperiness, mouthcoating
- Solid: Roughness, Hardness, Fracturability (force in which breaks), Cohesiveness, Tootpacking (sticks on teeth)
21
Q
What are some excipients used for sensory attributes?
A
- Propylene glycol: sweet/bitter (in high conc), oily and warming
- Glycerin: Sweet
22
Q
What are the requirements of acute pain relief medications?
A
- Rapid onset within mins (tablets take hours)
- Rapid drug dissolution
- Rapid drug absorption
- Minimal effort to take
23
Q
What are the disadvantages of oral medicines?
A
- 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
24
Q
What are the 3 different oral quick relief formulations?
A
- Oromucosal Absorption: Sublingual (under tongue), Buccal (inside cheek)
- Dispersible: Disperse in water then drink
- Orodispersible: Dissolve in saliva then swallow
25
What are the advantages of Sublingual and buccal formulations?
* Rapid onset
* No swallowing
* Mild oromucosal environment avoids drug degradation
* No first pass metabolism -> good bioavailability
26
What are the disadvantages of sublingual and buccal formulations?
* Potential unpleasant taste
* Salivary washout (drug needs to stay to get absorbed)
* Interferes w/ eating and drinking
27
What are the advantages of dispersible formulations?
* Rapid onset - dissolution outside of body
* Taken as a liquid, mitigating issues w/ swallowing and choking
* Improved bioavailability
28
What are the disadvanatges of Dispersible formulations?
* Potential unpleasant taste
* Potable water requirement
29
What are the advantages of orodispersible formulations?
* Rapid onset
* Overcomes issues w/ swallowing and choking
* No potable water requirement
* Improved bioavalability
30
What are the disadvantages of orodispersible formulations?
* Potential unpleasant taste
31
What are formulation considerations for oral quick relief formulations?
* 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
32
What are the different layers of the oro mucosa and what layer does it need to reach to get absorbed?
* Main keratinised barrier (oral epithelium)
* Basement Membrane + Lamina Propia
* Sub mucosa (contains blood vessels) - needs to reach to be dissolved
33
Where are each of the salivary glands (Parotid, Sublingual, Submandibular) located?
* 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
34
How does the drug from the mouth enter bloodstream?
* 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.
35
What are the characteristics of fentanyl?
* Lipophilic and Basic Drug
* Usually as salt (fentanyl citrate) - more water soluble so dissolved quickly
* Suscepitible to First pass hepatic metabolism
36
What are the characteristics of mucus and what is its function?
* Gelatinous layer surrounding oral epithelial cells
* Composition: Water & Mucin
* Negatively charged at physiological pH
* Provides lubrication, permeability barrier (Needs to cross for absorption) and anti microbial protection
* Drug can stick and helps with retention
37
What are the disintegrants in effervescent (dissolve and fizz) formulations?
* Carbonate Salt
* Bicarbonate Salt
* Citric Acid
38
Name some sweetners used in formulations?
* Sorbitol
* Saccharin sodium
* Lemon flavour
* Mannitol
* Aspartame
39
How are orodispersible tablets formulated?
* Designed to be porous, pockets filled w/ air. Water gets in by capillary action. Air isnt strong in holes so less hard - easier to dissolve
* Produced by lyophilisation
40
What are superdisintegrants and name some examples?
* Crosslinked polymers - can increase in vol when in contact w/ water - rapid extensive swelling
* Crospovidone
* Sodium starch glycolate
41
What is the process of lyophilisation?
* Freeze drying
* Rapid freezing: Water freezes into ice
* Primary drying: Ice sublimes directly into water vapour without melting
* Secondary drying: Desorption of residual moisture
* Dissolve quickly and leave voids and dissolves quickly
42
What are the 2 ways patches deliver drugs through the skin?
* Transdermal - systemic - extended release. Dermis layer than circulation
* Transcutaneous - topical - delivers locally. Straight from skin into tissues and muscle. Shorter duration
43
What are the advantages of patches?
* Avoids hepatic first pass metabolism
* Non-invasive - needle phobia (more acceptable)
* Extended release
* Easily applied and removable (unlike implants), can remove if ADR
44
What are the disadvantages of patches?
* Low deliverable doses (skin is barrier)
* Skin irritation - non-bio plastics and adhesives can be allergic to
* Variable absorption - sweat, wrinkle, thinner, drier, temp
45
What are the main components in a patch?
* Release Liner: Flap you remove before applying. Protects adhesive and contamination
* Adhesive: Sticks to skin, contains drug (in simple)
* Backing layer: Protects formulation, prevents occlusion (shield, covers volatile solvents from evaporating)
* Reservoir and Matric patches (more complex) - these contain drug. Matrix controls drug release - extended release
46
What are some excipients used in the drug matrix and backing layer?
* Drug matrix: Dipropylene glycol, hydroxypropyl cellulose
* Backing layer: PET film
47
What are the layers of the skin?
* Stratum Corneum (epidermis) - dead, metabolically active (lots of enzymes), corneocytes, most outer layer, extracellular lipid matrix
* Dermis - Blood vessels and nerve endings
* Hypodermis - fatty tissue
48
What type of drugs are more likely to be best absorbed?
* <500 Da - small
* log P 1-4 moderately lipohilic
* Several mg/ day
49
What are the similarities and differences between different strengths of the same patch?
* Release rate is greater as it increases overall.
* However fentanyl content per patch surface area is the same. 1cm3 contains same amount as other strengths
* Release rate per patch area is the same
50
What are the different diffusion pathways?
* Transcellular: Crosses straight through layers of cells
* Paracellular: Crosses around cells
* Appendageal : Through hair follicles and sweat glands
51
What do the abbreviations Kp, D, K, h, A and J stand for?
* Kp - Skin permeability coefficient
* D - Diffusion coefficient
* K - Skin partition coefficient
* h - Diffusion path length
* A - Diffusional Surface Area
* J - Flux
52
How do you test for dermal drug absorption in vitro?
* Franz diffusion cell
* Donor Chamber (drug), skin layer in between, Receptor chamber
* Quantifies how much drug has crossed in time - absorption rate
53
Why is there a lag phase in dermal drug absorption?
* Can be a few hrs
* Establishes drug diffusion path - no drug gets through
* Takes time to get from top-bottom
54
Why is there a depletion or non-sink conditions in dermal drug absorption?
* Reservoir is depleted - conc gradient drops and no driving force (plateau)
* Or drug accumulates in the skin - should keep near 0. Conc gradient drops
55
What is flux?
* Describes the absorption rate amount absorbed per unit time per surface area
* Same formulation flux should be the same
