Paeds Flashcards
What is the paediatric population important? (5 points)
- one size does not fit all
- kids cannot be treated as little adults
- they require dosing calculations (body surface area, weight)
- cannot extrapolate adult doses to children
- they have variable PK and PD profile of drug depending on developmental stage of the child
What are the main considerations in paediatric drug delivery? (7 points)
- accurate, flexible dosing schedule
- age range
- acceptability
- compliance
- stability
- ease of compounding & administration
- CR, desirable PK
What must be considered for a drug to be acceptable by a child? (4 points)
- pain
- taste/palatability
- frequency
- acceptable dose uniformity
What must be considered to achieve compliance?
-compliance and convenience of patient and caregiver
What must be considered in stability? (2 points)
- physical, chemical and microbial stability
- effect of excipients
What must be considered in ease of compounding & admin? (2 points)
- safe excipients
- safe and easy administration
Why is CR and desirable PK important?
-to achieve sufficient bioavailability
What is the clinical evidence in children like? (4 points)
generally lacking due to
- heteregenous population (physiology)
- small segment market (~15%)
- difficulties in controlled clinical studies, (ethical issues)
- formulation challenges
What are the preferred dosage form for infants 1 month - 2 years old?
liquids in small volumes e.g. syrups, solutions
What is the preferred dosage form for children 2-5 years old?
-liquids and effervescent tablets
What is the preferred dosage form for children 6-11 years old?
-solids including chewable tabs, orally disintegrating tabs
What is the preferred dosage form for adolescents 12-18 years old?
-solids like tablets and capsules
What is the age generally considered for a child to safely swallow a solid oral dosage form?
6 years old
What are the formulation development factors that should be considered? (3 points)
- efficacy and ease of use
- patient safety
- access of patient to medicines
What criteria must a product meet to achieve efficacy and acceptability? (3 points)
- dosage (flexibility)
- easy preparation/administration
- compliance (minimal impact on lifestyle)
What criteria must a product meet to achieve patient safety? (3 points)
- adequate bioavailability
- minimal, tolerable excipients
- stability during shelf life and in use
- minimal risk of dosing error
What criteria must a product meet to achieve adequate patient access? (3 points)
- robust manufacturing process with commercial viability
- Affordable (acceptable cost to patient, and payers
- easily transported and stored, low environmental impact
Why should the oral delivery route be considered? (5 points)
- swallowing abilities vary greatly across ages
- solids vs liquids have diff properties
- frequency of administration can be a challenge
- taste masking can be difficult
- novel delivery systems have potential
What is “Rubifen”? (4 points)
- Methylphenidate
- used for tx of ADHD
- immediate release often requires morning & midday dose difficult when at school
- CR formulation requires OD dosing
What are some approaches to taste masking? (5 points)
- Numbing/blocking taste buds
- Obscuration of taste
- Modification of API
- Creating molecular barrier around API
- Applying physical barrier on API
How can taste be obcured? (3 points)
- increasing viscosity
- adding sweetners/flavourants
- mixing with food
How can the API be modified? (2 points)
- changing the solubility (salt, pH)
- pro drug
How can a molecular barrier be created around the API?
-complexation using ion exchange resins or cyclodextrins
How can a physical barrier be applied around the API?
-using polymeric and lipidic coatings
What are the limitations with the oral route? (4 points)
- solid dosage forms often available but may be inappropriate
- Px may have difficult doses (1/3 of a tablet)
- swallowing difficulties
- liquid dosage forms may be unavailable
What happens if liquid dosage forms are unavailable?
- requires extemporaneous compounding
- liquid for inj, disp tab, formulating suspensions
- need to consider stability, accuracy and taste
What is extemporaneous compounding?
-manipulation of drugs & chemical ingredients with use of traditional compounding techniques to produce medications suitable for patients when no commercial forms are appropriate
What are the advantages and disadvantages of oral liquid dosage forms in paediatrics?
+liquid formulations viewed as the gold standard
+accurate dose can be administered in an easy to swallow form
+formulating suspension can improve Px compliance
-taste is a major obstacle to compliance
-choice of appropriate vehicle is important
What is the nipple shield device? (3 points)
- modified silicone nipple shield
- has an insert containing the API
- also has lips to hold the insert
How does the nipple shield device work? (4 points)
- uses milk as a vehicle for the administration of drugs
- designed to accommodate drug-loaded insert delivering API into milk while breastfeeding neonates
- lipid based vehicles provide solubilisation of highly lipophilic drugs
- Self emulsifying DDS can be prepared as solid dosage forms for reconstitution (milk = emulsion)
What is dose sip technology? (4 points)
- consists of a straw containing spheroids
- spheroids are neutral tasting
- liquid permeable controller supports spheroid transport during sipping, enables final check whether dose has been delivered to Px
- cap closes the system at the top
How does the dose sip technology work? (4 points)
- contains premeasured ready to use medicine with taste masking (coated with spheroids) and potential for SR
- drug initially in solid form improves stability
- drug is delivered as the Px uses the draw to drink liquid.
- e.g. Clarosip containing clarithromycin
What are fast dissolving drug delivery systems? (4 points)
- designed to disintegrate/dissolve once in contact with saliva
- may dissolve over a few seconds to 1 minute
- drug may absorb from oral cavity or from GIT as dissolved drug is swallowed
- need to consider taste masking
What are the advantages with FDDDS? (5 points)
+excellent dose flexibility
+water not required
+avoids swallowing
+preferred over conventional formulations
+continuous manufacturing can be achieved
What are the disadvantages with FDDDS? (8 points)
- CR and taste masking is challenging
- excipients of unknown safety profile may be required
- specialised packaging required
- retention time in mouth alters bioavailability
- uniformity of dose challenging
- only low doses can be incorporated
- technology subject to intellectual copyright
- uses solvent based manufacturing process
What is Benznidaole? what is chagas disease? (5 points)
- drug indicated for Tx of Chagas Disease
- Chagas disease affects 8-10M ppl worldwide, kills 12K ppl annually
- transmitted during pregnancy from infected mother to baby
- children are at high risk of infection
- Tx in first year of life eliminates the parasite from 90% of newborns
What are the limitations with conventional Benznidazole formulations? (4 points)
- previously only available as 100mg tablet for adults
- dosing is 5-10mg/kg/day
- treatment for young children requires compounding and administered BD for 60 days
- improper dosing, increased S/Es, ineffective Tx, stopping Tx
What are the advantages of the new formulated Bnznidazole treatment? (2 points)
- new 12.5mg tab is easily dispersed
- indicated in Px up to 2 years of age
What is EMLA? (4 points)
- contains lignocaine 2.5% and prilocaine 2.5%
- sufficient application time is required
- used in vaccines to ease discomfort
- although EMLA acts on local blood vessels, vaccines are still effective in promoting protective levels of antibodies
What formulations is EMLA available in? (3 points)
- cream (5x5g or 30g tubes)
- patches (1g patch in packs of 2 or 20)
- AstraZeneca Ltd
What is Bioject? (4 points)
- liquid medicine formed at high speed through tiny orfice held against the skin
- designed to deliver accurate dose of medicine with minimal or no discomfort without using a needle
- can deliver subcut, IM
- skin and injector are swabbed with alcohol prior to injection
How does Bioject work? (4 points)
- uses high pressure CO2 to pierce the skin
- medication dissipates over greater area compared to needle stick
- during injection, Px will feel some pressure
- localised redness and tenderness may follow
What is the pulmonary delivery route? (4 points)
- large bloodflow and SA
- predominantly for local delivery, but has potential for systemic delivery
- some dosage forms are difficult for younger Px to understand and coordinate
- preparations for inhlation include liquids for nebulisation, MDI, DPI
What is a metered dose inhaler? (3 points)
- pulmonary pressurised delivery device
- contains active drug, propellant and cosolvent in the container
- when pushed, the actuator seal releases a set dose of drug through the nozzle and out via the spray orfice.
What are the challenges of pulmonary delivery? (3 points)
- need to consider implications of physiology of children
- limited by their ability to use devices correctly (coordination problems)
- total lung deposition is important for clinical effect (affected by formulation and delivery device controlling size distribution of aerosol)
What is the issue with ethanol in paediatric medicines? (4 points)
- WHO wants safe and effective meds for children
- excipients are usually biologically inert, but some do have biological effects
- ethanol is used in some liquid medicines as solvent, preservative and sometimes as an active
- safety concerns regarding ethanol use (case reports and anecdotal evidence)
What are examples of ethanol used in formulations? (3 points)
- Elixirs: clear, sweetened hydroalcoholic liquids with alcohol content ranging from 5-40% v/v e.g. antihistaminic elixirs
- Digoxin contains 10.1-11.4$ v/v ethanol, used in Px of all ages at small quantities with unknown effect. Unsure of chronic exposure implications
- Oral gel for teething and mouth ulcers for general sale should have “this preparation contains alcohol” as can have 38-76% v/v ethanol
