Formulation approaches to pediatric oral drug delivery: benefits and limitations of current platforms

Figures & data

Table 1. List of requirements for age-appropriate oral drug delivery systems.

Benefit/risk	Criterion for drug product	Product requirements
Efficacy/acceptability	Dosage	Dose flexibility Acceptability of size/volume
	Preparation/administration	Easy and convenient handling Easily administered (correct use)
	Compliance	Minimal impact on lifestyle Acceptable appearance and taste Minimal administration frequency
Patient safety	Bioavailability	Adequate bioavailability
	Excipients	Minimal number of excipients Tolerability
	Stability	Stable during shell life Stable in-use
	Medication error	Minimal risk of dosing error
Patient access	Manufacturability	Robust manufacturing process Commercial viability
	Affordability	Acceptable cost to patient and payers Easily transported and stored Low environmental impact

Data taken from [9].

Figure 1. A range of formulations and devices for age-appropriate oral drug delivery, which have emerged during the past two decades. Green triangles above: commercialized dosage forms and devices; Blue triangles below: non-commercialized dosage forms and devices. This is not intended to be an exhaustive list but exemplify progress.

Figure 2. Schematic illustration of the nipple shield device (left) and image of a prototype device including drug delivery insert (right).

Table 2. Advantages and disadvantages of multiparticulates for the preparation of age-appropriate products.

Product characteristic	Advantages	Disadvantages
Efficacy/acceptability
Dosage	Excellent flexibility of dose Small size/swallowing is aided	Grittiness/mouthfeel may be an issue
Preparation	Flexibility of administration	Need for preparation/reconstitution
Compliance	Ease of functionalization Suitable for taste masking
Safety profile
Bioavailability	Highly reproducible due to uniform GI transit Targeted release profiles can be achieved	Co-administration with food/drinks may alter bioavailability
Excipients	Use of Generally Regarded As Safe (GRAS) excipients
Stability		Food-drug compatibility needs to be studied
Medication error		Limited control over dose intake when mixed with food
Patient access
Manufacturability		May need specialize equipment or accessories
Affordability	Manufacturing technology readily available	Need to develop packaging/dosing technology platform

Figure 3. Dose sipping technology: prototype straw containing granulated product with removable cap (left) and without cap, ready-to-use in a glass of water (right).

Table 3. Advantages and disadvantages of orodispersible tablets for the preparation of age-appropriate products.

Product characteristic	Advantages	Disadvantages
Efficacy/acceptability
Dosage		Various dosage strengths required
Preparation	Water is not required Swallowing is avoided Flexibility of administration	Lack of mechanical strength
Compliance	Preferred over conventional formulations	Controlled-release is challenging Taste masking is challenging
Safety profile
Bioavailability	May be improved by buccal absorption
Excipients		Excipients of unknown safety profile may be required
Stability		Packaging and storage conditions can be critical
Medication error		Retention time in mouth may alter bioavailability
Patient access
Manufacturability		High doses may not be incorporated
Affordability		Technologies subjected to intellectual property rights

Table 4. Advantages and disadvantages of orodispersible films for the preparation of age-appropriate products.

Product characteristic	Advantages	Disadvantages
Efficacy/acceptability
Dosage	Excellent dose flexibility
Preparation	Water is not required Swallowing is avoided
Compliance	May be preferred over conventional formulations	Controlled-release is challenging Taste masking is challenging
Safety profile
Bioavailability	May be improved by buccal absorption
Excipients		Excipients of unknown safety profile may be required
Stability		Specialized packaging often required
Medication error		Retention time in mouth may alter bioavailability
Patient access
Manufacturability	Continuous manufacturing can be achieved	Uniformity of dose may be challenging Only low doses can be incorporated
Affordability		Technologies subjected to intellectual property rights Solvent-based manufacturing process

Figure 4. Examples of orodispersible films in single-dose (left) and multiple-dose (right) packaging alternatives.

Table 5. Advantages and disadvantages of chewable tablets for the preparation of age-appropriate products.

Product characteristic	Advantages	Disadvantages
Efficacy/acceptability
Dosage		Various dosage strengths required
Preparation	Water is not required Swallowing is avoided
Compliance	May be preferred over conventional formulations	Controlled-release is challenging Taste masking is challenging
Safety profile
Bioavailability	May be improved by quick disintegration and dissolution May be improved by buccal absorption	Bioavailability may be altered depending on chewing ability
Excipients		Excipients of unknown safety profile may be required
Stability		Soft-chews may be problematic due to water content
Medication error		Retention time in mouth may alter bioavailability Possible overdose if misused as confectionary
Patient access
Manufacturability		May need specialize equipment or accessories
Affordability	Manufacturing and packaging technology readily available

Sam T, Ernest TB, Walsh J, et al. A benefit/risk approach towards selecting appropriate pharmaceutical dosage forms - an application for paediatric dosage form selection. Int J Pharm 2012;435(2):115–23

 PubMed Web of Science ®Google Scholar

JustMilk. Safely delivering drugs and nutrients to breastfeeding infants. Available from: http://www.justmilk.org [Last accessed 04 June 2015]

 Google Scholar