Paediatric formulations

Question 1

What is the importance of formulation preferences and the different formulation requirements?

Answer 1

Paediatric practice requires a rand of dosage forms that are acceptable at different ages and abilities and a range of strengths or concentrations allowing administration of the correct age related dose. Depending on the severity of the condition,different dosage forms can be given in different ways.This is due to the bioavailabity of the dosage form.

Question 2

What are the differing conditions for preterms/neonates?

Answer 2

Drug can not be given via an oral route since ther is an inability to swallow so, drugs routinely given by injection,suppositories or nasogastrically. There may be physical/chemical interactiosn with feed/other drugs and possible decreased serum drug concentration – so dose adjustment may need to be made here.Amiodorone and certain ppis – omeprazole most variable.

Question 3

What is the differing requirement for infants and who would you actually class an infant?

Answer 3

Drugs can be given via the oral route by syringe/crushed powder crushed tablet added to drink or liquid(administered using asyrineg or as an emulsion)

Question 4

What is the requirement for children and who would you consider a child?

Answer 4

drugs can be given as a liquid or a suspension, age of 6 may be able to swallow tablet.depends on the size and shape of the tablet and the acceptability
Tablets generally easier and cheaper to manufacture,store and dispense than liquids.powder sachets and granules,solauble tablets can also be given as aviable option to liquid.

Question 5

What is the requirement for seriously ill patients?

Answer 5

IV route is used for chronically ill, but less seriously pt oral is used.Buccal and nasal transdermal and rectal routes may be sued of no oral dosage forms are available.

Question 6

What is the flow diagram for the dosage form :

Answer 6

Is the route acceptable, is it stable? Chemically and is it soulable?

Question 7

What is improving acceptability and why is it so important?

Answer 7

Avoiding unsual flavours – most common in Uk berry, Liquirice in scandenavia and bubble gum and grape in America. Children prefer high levels of sweetness, than adults so using sucrose,aspartame may help.Sucrolose may be used by should be avoided long term.Few dyes are available, for regulatory purposes – use of dyes should be limited to avoid hypersensitivity.Smooth texture is preffered so viscosity needs to also me monitored.

Question 8

What are specials and when would we use them?

Answer 8

A licensed drug is used for by unlicenced use,indication,dose or agelimits.

Question 9

Explain the specials flow diagram in details and each step that is involved?

Answer 9

Is the drug licensed for paediatric use? Yes – liquid drug from available, no drug from – then manipulate solid to obtain liquid form – special or extremporaneous preparation. No- liquid drug form available off label use.

Question 10

When would you use a special?

Answer 10

If there is no clinical friendly formulation, adult formulation may be manipulated eg.crushing a tablet,opening a capsule and

wixing contents with food or drink. Manipulating adult formulation is
problematic because of stability issues and dosing is not assured.

Question 11

How many children use an off- label medicine?

Answer 11

50-90% - medications used in
children one off- label or unlicensed.Therefore, children are being treated in evidence based,unregulated fashion.Even commonly prescribed drugs eg.short acting beta – 2 antagonist and anti pyretics have not been adequately studies in young children as per hay et al 2006)

Question 12

What are the steps of license medicines?

Answer 12

Steps – Licensed drugs + licensed use, licensed drug + off label – use, Unlicensed use special.

Question 13

What is the issue with using specials?

Answer 13

Limited enrolment in trials means that there is an inability to demonstrate efficacy and safety in all paediatric patients and sub population.This is due to a small number of volunteers and issues relating to the ethics of testing in healthy children,results can be extrapolated from adults or paediatric groups of different ages. But this can lead to dangerous due to pharmokinetic variations.Development pf paediatric formulations is rarely commercially viable .This is because diseas may be rare and so it is not cost effective to be manufacturing a drug that is rarely used.

Question 14

What are the regulatory incentives in place?

Answer 14

Eu regulation on paediatric meds aims to encourage pharmaceutical companies to consider the paediatric population, drug development and maketing objectives.

Question 15

What is a brief list of Pharmacokinetic variation?

Answer 15

• Increase development development of paediactric medicines
• Ensures medicines are subject to high quality research and appropriately, authorised
  use in children,improve amount of it in the formulation that is available,Achieve the above without the need for unnecessary trials or delaying authorisation of adult drugs.

Question 16

Explain the features of absorption:Explain the feature of oral

Answer 16

Gastric ph is 6-7, unionised form dissolves ad is absorbed, therefore the higher th PH increases the bioavailability of basic drugs and weakly acidic drugs. As a consequence, the dose of basic drugs should be reduced until the age of 2 to avoid toxicity and over dose.The dose of acidic drugs should be increased. Bile salt formation is decreased until 6 months bioavailabilty of lipophilic drugs is reduced, an increased dose is required for these drugs.

Question 17

Explain the feature of IM

Answer 17

Decreased blood flow so absorption is slower.there are fewr muscular contractions,decreasing dispersion of the drug.

Question 18

Explain the feature of Rectal

Answer 18

more pulsatile contractions moving the suppository from the body so decreases absorption.

Question 19

Explain the feature of transdermal

Answer 19

babies and newborns and kids have a large BSA:mass ratio, the skin is thinner and there is a greater bloody supply to the ksin so the absorbtion is increased so greater side – effects may be seen.

Question 20

Explain the features of distribution

Answer 20

Neonates and infants have a higher proportion of water compared to fat.This affects how water soulable drugs are distributed and and causes a lower plasma concentration,higher doses of water soluable drugs are needed. There are lower levels of albumin so highly protein – bound drugs given lower doses.

Question 21

Explain the features of Metabolism?

Answer 21

Rate of metabolism appears to be highly age dependent – slower for first year, exceeding adult metabolism rates during childhood, and finally attaining adult rates during adolensnce.

Question 22

Explain the features of elimination

Answer 22

Many drugs are renally excreated therefore functioning of the kidney largely determines how quickly a drug is cleared from the body. eGFR- increased rapidly during the first 2 weeks of life life due to changes in blood flowand maturing reproduction hormones. Continues. To increase as children gets older stops increased at around 6 years old.

Question 23

What is an example of ADHD medication?

Answer 23

Methylphenidate- ADHD meds - Ideal properties of ADHD medication are : long duration of action, ease of administration,rapid onset of action
- Methylphenidate has short half life and multiple doses poses issues, reducing compliance,inconvenience,social stigma,sensitivity issue.

Question 24

What are the key features of ADHD Medication?
26. Explain the features of the medication

Answer 24

Concerta XL capsules – immediate
release component (22% of the dose), outer coating is absorted rapidly after ingestion.Modification component – 78% of the dose.Penetration of the gastric fluid through semi-permiable outer membrane expands an osmotic agent, in the push layer of the core,causing it to slowly force the methyl phenedate contained in the core out of a laser hole opening in the capsule over a 12 hour period. Total dose of 15mg of standard release formulation is bioequivielent to concerta 18mg once daily.

Question 25

Draw and label a diagram of before and after?

Answer 25

Rate controlled membrane

Question 26

What are the main issues with paediatric adherence?

Answer 26

Compliance refers to
whether patients takes their meds.Adeherence is the active and voluntary involvemnt of the patient in a mutually acceptable cause of behaviour to produce a therapeutic. Children lack rational thinking so they cant understand the decsison that they make- that something that taste bad has a long term benefit.So flavourings give a better likelihood of adherence.Liquids are also preferred to tablets – high overdose volume for liquids so much safer.

Question 27

What are the issues with liquid formulations?

Answer 27

Failure to shake – suspension not evenly distributed,unstable sue to water activity,susceptible to microbes contamination,hard to transport,expensive to manufacture,measuring accuracy- if volume is too small – inacc dose, if volume is too big = adherence issue.need for an excipient is a possible safety issue -alcohol as a co- solvent , taste masking – bad no eat – too good =to much eat

Question 28

What is the public opinion?

Answer 28

25% of parents show negative beliefs about meds = non adherence
Only 50% of people think its is a good idea for children to learn to take tablets and only 18% think pharmacist should help out in this,

Question 29

Method to improve adherence

Answer 29

masking in other food and drink, force , bribert

Question 30

Role of schools?

Answer 30

Since 2014 gov have statatury duty to make sure chools can
support arrangement under families act 2014.- don’t have to but should try and help – labelled and put into a container – only administered if not giving it would be detremental to health and attendance.