L7 - Age Formulations

Question 1

Oral liquids: Negatives - 5

Answer 1

1. Bitter taste of drugs: conceived as toxic agents
2. Major barrier is compliance due to bitter taste, so taste-concealing properties use
3. Excipients used for palatability, shelf-life, &/or manufacturing processes
4. Some excipients not used as can retard organ development e.g. ethanol, propylene glycol, & benzyl alcohol

Question 2

Oral Liquids - 3

Answer 2

1. provides maximal dosing flexibility
2. possible to use for a wide range of age range (including neonates)
3. volume needs to be acceptable to the patient & dosing device must be fit for purpose

Oral liquid doses – 4 & 12yrs
Max single dose:
5ml for children < 4 year olds
10ml for children 4 - 12 year olds

Question 3

Solids for reconstitution e.g. powders, granules, pellets or sprinkles - 5

Answer 3

1. More stable than formulated liquid
2. Reconstitution either at the point of dispensing or administration
3. Instructions can be complicated for untrained individuals
4. Liquid Vol > than vol for oral liquid
   up to 20 ml for children < 4 year old
   up to 50 ml for those > 4 year old)
5. Dispersible products: If not reconstituted in appropriate volume of liquid risk of local tissue injury or4 delay in onset of action (drug needs to dissolve prior to absorption)

Question 4

Oral solid dosage forms: Conventional tablets – 3

Answer 4

1. limited by rigid dose content & ability to swallow tablet
2. Smaller tablets more accepted by children
3. Mini-tablets were more readily swallowed by young children (6-12 months), & suitable for 2-6yrs

Question 5

Oral solid dosage forms: Capsules – 3

Answer 5

1. Capsules can be opened & the contents be taken to improve acceptability in children, but only when justified
2. But capsule content: Taste unpleasant & different BA than intact product
3. Below 250ml of water can delay onset of absorption & reduce BA of drugs (particularly poorly water soluble)

Question 6

Chewable tablets - 5

Answer 6

1. Many patients in long-term care have difficulty swallowing solid forms, so chewable is alternative
2. Disadvantages include the need for taste masking & relatively less stable than solid oral dosage forms
3. Chewed to produce pleasant tasting, easily swallowed residue
4. Can improve compliance
5. In children, especially under 2 years of age: risk of aspiration of chewable tablet if not chewed properly which could result in death of the patient.

Question 7

ODTs (Orodispersible tablets) formulations - 8

Answer 7

1. Many patients in long-term care have difficulty swallowing solid forms, so ODTs alternative as swallowing not required
2. Relatively less stable than solid oral dosage forms due to hygroscopicity
3. Take a min to dissolve, making them not sublingual tabs, buccal tabs or a lozenge
4. Tablet disintegrates in mouth, & API absorbed through pre gastric (i.e. oromucosal tissues), gastric (i.e. stomach) & post gastric (i.e. small & large intestines) segments of the GT. Variety of absorption routes can affect BA & safety profile
5. Formulated using very water-soluble excipients, such as sugars (assists in disintegration of the tablet)
6. Ease of administration increases patient compliance
7. Somes ODTs made via direct compression e.g. OraSolv use effervescent excipients to assist in disintegration
8. ODTs made via Lyophilisation disintegrate quickly due to API inside highly porous, water-soluble matrix

Question 8

GASTROINTESTINAL TRACT DEVELOPMENT - 4

Answer 8

1. Neonates have a higher pH after feeding due to lower HCl secretion, which lowers buffering capacity of stomach, which leads to extended high pH after feeding
2. Lower buffer capacity linked to increased BA of acid-labile drug, penicillin G
3. The higher pH means weak acids (e.g. phenytoin, rifampicin ) are less absorbed, whilst weak bases (e.g. atropine, caffeine) are more readily absorbed from the stomach
4. However, primary site of absorption is small intestine, & the pH resembles an adult’s from 6 months onwards

Question 9

GASTRIC EMPTYING TIME (GET) - 3

Answer 9

1. Gastric emptying times is prolonged in neonates & children relative to adults due to differences in food & contractions
2. Meal volume, osmotic pressure & composition of macronutrients have a major effect on gastric emptying e.g. fatty acid type affects rate of gastric emptying
3. i.e. slower emptying is observed after feeding with long-chain fatty acids compared to medium-chain triglycerides.

Question 10

Intranasal drug administration - 3

Answer 10

1. Convenient, fast onsets of action, similar action to IV, routinely used within paediatric populations.
2. Drugs delivered via several methods: instilled from a syringe, nebulised or given through a pressurized aerosol (all effective).
3. Similarities in anatomy & physiology ensure products likely to perform same in adults & children (few reported adverse effects).

Question 11

Occular drug delivery – 6

Answer 11

1. Eye membranes thin in neonates & infants, so drug absorption & corneal permeation may be more rapid in these groups, but have a smaller absorption SA
2. Topical application have high risk of serious adverse S/Es as ocular dose not weight adjusted
3. Especially vulnerable if drug metabolism is reduced, or has immature blood brain barrier
4. Increased systemic exposure observed in paediatric patients has been attributed to absorption of eye drops into the systemic circulation
5. Reduced size of the patient results in higher [plasma] of circulating drug.
6. Estimated: a newborn requires ½ adult dosage of eye drops to obtain an equivalent [ocular]: 2/3 adult dosage required at 3 years & 90% dosage at 6yrs

Question 12

Otic drug delivery - 4

Answer 12

1. Routinely used within paediatric populations for therapies of otitis externa, otitis media and the removal of ear wax.
2. Small vol used as excess lost out of ear passage.
3. Various anatomical & physiological changes occur with age, such as infant’s having smaller & straighter auditory canals
4. Dosing devices allow smaller doses to be administered in paediatric patients (no significant systemic uptake from medicines administered aurally).

Question 13

Rectal drug delivery - 3

Answer 13

1. Routinely used to treat both local & systemic disorders in children.
2. Useful for infants & children who have difficulty in swallowing oral medicine, or nausea & vomiting, or intestinal disorders which may affect oral drug absorption.
3. Rectal absorption surface area is an important factor to consider when treating systemic effects

Question 14

Dermal & transdermal drug delivery - 3

Answer 14

1. Higher levels of absorption may be reached in paediatric patients as stratum corneum is thinner, & more permeable.
2. SA:BM is higher in neonate than adult, so Vd is lower per unit area of skin within the paediatric population.
3. Excipients for such products need careful consideration (absorption of propylene glycol from an antiseptic dressing used in a preterm infant caused infant to become comatose, recovered once treatment stopped)

Question 15

Pulmonary drug delivery - 6

Answer 15

1. Airway size, respiratory rate, inspiratory/expiratory flow rates, breathing patterns, lung volumes & capacities change dramatically during the first months & years of life.
2. Nebulised liquids potentially suitable for young children who cannot use metered dose inhalers (MDIs) & dry powder inhalers (DPIs)
3. MDIs may be suitable for children from birth when combined with a spacer (i.e. eliminates need for the patient to co-ordinate actuation with inhalation).
4. Face mask required until child can manage with a mouth-piece.
5. DPIs useable for children from the age of 4-5 years, as minimum inspiratory flow is required.
6. MDIs & DPIs preferred for older children because of portability & convenience.