paediatric formulations

Oral liquids

Bitter taste of drugs

can be overcome with taste masking

using salt form or flavour excipients

to make it more appealing for children

considerations in oral excipients for children

no ethanol, propyl/benzyl alcohol can affect development

also salts can cause electrolyte imbalance

Oral dosing liquids

use syringes or spoons

max 5mls

max 10 mls in 4-12 years

Neonates: syringes is most accurate

Solid dosage form in terms of liquid

Use solids for reconstitution

• Dispersible tablets, powders, granules, pellets or sprinkles

Disadvantages:

risk of local tissue injury

delayed onset action of drug as it needs to be dissolved before absorption

oral dosage forms

smashing and cutting changes dissolution size

which can affect the dissolution rate and absorption

mini tablets

tablets smaller than 3mm

oral capsules

in its solid form not appropriate due to size in children

but its appropriate to open and dissolve the contents to improve acceptability

oral liquids advantages

• dose flexibility

• used for

chewable tablets

orally disintegrating

can overcome patients with dysphagia

route of delivery is via GI tract

disintegration is initiated in oral cavity and broken into smaller particle sized for absorption and dissolving in GI

Chewable tablets composition

Mainly mannitol

xylitol

not recommended for children under 2

Orodispersible formulations

Solid dosage form containing medicinial substances which disintegrates rapily on tongue

no need to chew NOT SAME AS SUBLINGUAL

difference between ODT and sublingual

àbuccal tablets and lozenges as they require at least more than a minute to dissolve in the oral cavity.

Metabolism of ODT

Tablets disintegrate in the oral cavity and the active pharmaceutical ingredient is absorbed through pre gastric (i.e. oromucosal tissues), gastric (i.e. stomach) and post gastric (i.e. small and large intestines) segments of the GI tract

ODT bioavailability

very water soluble to assist interaction with saliva for disintegration

formulated by compression, lyophilisation, moulding

also contains highly water soluble sugar such as mannitol, lactose, glucose, sucrose → risk of hygroscopicity needs to stored properly

What is lyophilisation

initiated by removal of water by

      sublimation of the liquid mixture of drug and excipients. The mixture is

      then freeze dried, to yield drug in a highly porous, water soluble matrix

makes it rapidly disintegrating

ideal for easy administration in young children and elderly

considerations with ODT

cost

hygroscopicity

volume of liquid taken

GI impact describe the pH

neutral gastric pH is 6-8 due to amniotic fluid

resting pH of neonates is pH 2 after feeding

Q: How does hydrochloric acid secretion in neonates compare to adults?

A: It is lower, resulting in a lower buffering capacity and prolonged high pH after feeding.

Q: How does the neonatal stomach's lower buffering capacity affect drug bioavailability?

A: It increases the bioavailability of acid-labile drugs like penicillin G in neonates < 2 weeks old.

Q: How does a higher gastric pH affect weak acid drug absorption?

A: It decreases the rate and/or extent of absorption of weak acids (e.g., phenytoin, rifampicin).

Q: How does a higher gastric pH affect weak base drug absorption?

A: It enhances absorption of weak bases such as atropine, caffeine, and other methylxanthines.

Q: What is the primary site of drug absorption in neonates?

A: The small intestine.

Q: How does small intestinal pH in neonates compare to adults?

A: Data on neonates is unavailable, but from 6 months of age, the fasting small intestinal pH is similar to adults.

Q: How does gastric emptying time (GET) in neonates and infants compare to children and adults?

A: GET is prolonged in neonates and infants.

Q: What is the approximate volume of stomach contents in the fasted state for different age groups?

• Neonates & infants: ~3 ml

• Children: ~10 ml

• Adults: 50-222 ml

Q: By how much can stomach content volume increase after feeding?

A: It can increase up to 50-fold.

Q: What factors influence the rate of gastric emptying?

A: The volume of a meal, its osmotic pressure, and its macronutrient composition.

Q: How do fatty acids affect gastric emptying in infants?

A: Long-chain fatty acids slow gastric emptying more than medium-chain triglycerides.

Q: Why is gastric emptying time (GET) prolonged in neonates and infants?

A: Due to differences in food type and weaker gastric contractions (less pronounced in neonates than in infants).

How does pepsin activity differ in paediatrics

The secretion of pepsin is increased 3 -4 x during gestation

pepsin is low in preterm neonates

secretion of pepsin gradually increases

how does bile levels differ

Bile is a complex fluid, containing water, electrolytes and bile acids, phospholipids, cholesterol and bilirubin.

Bile aids the solubilization of the poorly-water soluble products of lipid digestion, e.g. fatty acids, as well as enhancing the solubility of poorly water soluble drugs.

Can act as a surfactant

exhibit low bile secretion so reduced absorption of fat soluble vitamins e.g. vitamin D and E

Nasal dug delivery in paediatrics benefits

àConvenient with fast onsets of action , its action close to that of

      intravenous therapy

no differences in nasal mucus, pH or mucociliary clearance in paediatric patients

Q: What are the common types of ocular medicaments used in children?

A: Drops, ointments, gels, and inserts.

Q: What conditions are treated with ocular medicaments in children?

A: Bacterial and viral infections, inflammation, allergy, uveitis, glaucoma, and myopia.

Q: When does the eye reach adult size?

A: Around ages 3 to 4 years.

Q: How does drug absorption in the eye differ in neonates and infants?

A: Membranes are thinner, leading to faster drug absorption and corneal permeation.

neonates have 70% absorption of adult cornea but low intraocular volume can lead to systemic effects

Why can there be side effects through occular delivery

A: Ocular dosing is not weight-adjusted, leading to a higher systemic drug exposure.

A: Due to immature drug metabolism and an underdeveloped blood-brain barrier.

overall anatomical and physiological differences vulnerable to systemic effects

Octic delivery in paediatric population

small volume is used due to excess liquid lost in

used for otitis externia/media/ear wax removal

Q: How is the anatomy of the outer ear different in infants compared to adults?

A: The external auditory canal (EAC) in infants is straighter, narrower, and much shorter than in adults.

EAC volume increases with age

Q: Why are dosing devices important for paediatric patients receiving ear drops or sprays?

A: Dosing devices allow smaller doses to be administered, as there is no significant systemic uptake from medicines applied aurally.

Q: What types of therapies are routinely used to treat both local and systemic disorders in children?

A: Creams, ointments, suppositories, foams, sprays, and enemas.

Q: Why is the rectal route particularly useful for infants and children?

A: It is helpful for children who have difficulty swallowing oral medicine.

Q: In what cases is the rectal route beneficial for drug delivery?

A: It is useful for nausea, vomiting, or situations where upper intestinal disorders affect oral drug absorption.

Q: How does the rectum’s size and shape change with development?

A: The diameter, length, and volume of the rectum change during development, reaching adult dimensions at about 10 years of age.

changes in surface area- affects absorption

weight, height, body

monitor for systemic side effects

Q: How does the skin change during development, and why is this important for paediatric formulations?

A: The skin undergoes many changes, and these changes affect how paediatric formulations are absorbed and utilized. For example, the stratum corneum is intact shortly after birth, but water storage and transport become more adult-like after the first year of life.

Q: How does the surface area to body weight ratio in neonates compare to adults, and what does this mean for drug distribution?

A: The surface area to body weight ratio is much higher in neonates than in adults, leading to a lower volume of distribution per unit area of skin in the paediatric population.

Q: What types of preparations are used for dermal administration in paediatric patients?

A: Liquid preparations (lotions and shampoos), semi-solid preparations (ointments and creams), and solid preparations (powders).

Q: Why do paediatric patients need careful consideration when using topical agents?

A: While these products are generally considered safe, higher levels of absorption can occur in paediatric patients, particularly if the skin is broken.

Q: What are some common topical agents used for newborn infants?

A: Newborn infants are commonly exposed to topical agents for treating rashes, antimicrobial agents, solvents, and skin barriers or moisturizers.

Q: Why must the excipients in topical products for paediatric patients be carefully considered?

A: Excipients need to be carefully considered because substances like propylene glycol can be absorbed through the skin. For example, its absorption from an antiseptic dressing caused a preterm infant to go into a coma, though full recovery occurred after discontinuation of the topical treatment.

Q: What conditions are commonly treated with inhaled medications in infants and small children?

A: Asthma and cystic fibrosis.

Q: How do airway size, respiratory rate, and lung function change during early childhood?

A: These factors change dramatically during the first months and years of life, including airway size, respiratory rate, inspiratory/expiratory flow rates, breathing patterns, and lung volumes and capacities.

Q: How are delivery devices for inhaled medications modified for infants and small children?

A: Devices are similar to those used by adults but are often modified by attaching a small infant or child-sized mask.

Q: Why are nebulised liquids particularly suitable for young children?

A: Nebulised liquids are suitable for young children who cannot use metered dose inhalers (MDIs) or dry powder inhalers (DPIs) perhaps if minimum inspiratory flow is not reached

Q: When can MDIs be used in children, and what modification makes them suitable?

A: MDIs may be suitable for children from birth when combined with a spacer, which eliminates the need to coordinate actuation with inhalation.

Q: How is the dose of inhaled medications typically adjusted for children?

A: Dose adjustments for inhaled medications are usually based on body weight, with extrapolation from adult doses being acceptable for children aged 3-12 years.