Pharmaceutical Outsourcing Q2 2024 - 28

ROUNDTABLE
formulation has been optimized, the drug product can progress
to patient studies to assess the efficacy in the target disease
population. This can present new challenges that put a strain on
traditional product manufacturing and supply logistics, something
we see often in the development of therapies for rare diseases.
LaBella: There are several factors that impact these points. Dose is
probably the most significant factor. A high dose of drug will usually
be more difficult to formulate into a palatable product. This may be
driven by taste or mouthfeel. Solutions are a common basic platform
used for many pediatric products but may offer the worst palatability
for a really bad tasting drug. Formulation of a suspension product can
help improve taste over a solution. As you would expect, suspensions
are more complex and require different manufacturing equipment.
Other techniques such as using ion exchange resin or encapsulation
or taste masking coatings, create more challenges in manufacture
including use of organic solvents in some cases. Ingredients must be
scrutinized for safety in the pediatric population as well, especially for
medications taken for chronic conditions.
How do you address the issue of
dose accuracy and variability in
pediatric formulations, considering the
diverse age groups and physiological
differences among children?
Shanmugam: Addressing dose accuracy requires a precise and
multi-faceted approach that considers the diverse age groups and
physiological disparities among children. Dose accuracy can be
achieved with the following strategies:
1. Patient Characteristics (sp. population pharmacokinetics):
This provides crucial insights into how drugs are metabolized in
children and guides precise dosage adjustments based on factors
like age, weight, and developmental milestones. Collaborating
with pediatric clinical experts ensures the incorporation of their
specialized knowledge into formulation design, contributing to
safer and more effective medications for children.
2. Formulation Strategies: This helps experts design dosage forms
that are tailored to specific age groups, as well as formulations
that can offer flexible dosing while taking into consideration
factors like a child's ability to swallow, their preferences, and the
need for age-appropriate formulation applicability (such as oral
liquids, chewable tablets, or dispersible tablets.) Formulations
for flexible dosing should be easily adjusted based on a child's
age, weight, and specific medical needs.
3. Patient-centric Dosing Tools: Accuracy can be achieved by
developing tools for dose measurements and application, such
as oral syringes for multiparticulates, minitablet dispensers, etc.
Any dosing tool with clear markings or ability to dose precisely
will enhance the accuracy.
Kanji: Dosing is generally done in bands that are based on age,
weight, or body surface area, with oral liquid formulations and
minitablets among the most popular choices for their acceptability
and efficacy in younger patients. Modeling and simulation can also
be used to aid dose extrapolation from adult data and predict the
in-vivo performance of a dosage form in children.
LaBella: The easiest way to resolve this concern is the use of liquid
platforms. The quantity of solution or suspension is easily modulated
using a dosage syringe to offer the most appropriate dose of a drug
to a patient based on their age or body mass.
How do you prioritize patient-centric
approaches in pediatric dosage form
development to ensure compliance and
minimize treatment-related challenges
for children and caregivers?
Shanmugam: A myriad of factors-including patient characteristics,
product characteristics, clinical trials, caregiver characteristics-
reflect the diverse needs of pediatric populations. Unfortunately,
addressing each single factor or need is impractical. Prioritizing
essential factors with significant impact on improving acceptance
and adherence of medicines is a more practical approach. Dose
convenience and dose flexibility are two key contributors that need
to be prioritized for maximum benefits.
This typically involves optimizing palatability through taste-masking
technologies and ensuring age-appropriate formulations that align
with developmental stages. It also entails providing dosing and
administration tools that are friendly to patients and caregivers
and facilitate accurate dosing. Similarly, prioritizing flexible dosing
options to accommodate varying dosing needs, such as weightbased
or age-based dosing, is also crucial.
Additionally, caregivers' input in pediatric-focused clinical trials
is essential but often neglected. Engaging pediatric patients and
caregivers in the development process allows for valuable input,
ensuring formulations meet their preferences and needs. Similarly,
conducting pediatric-specific clinical trials with a focus on patientreported
outcomes ensures that the experiences and preferences of
children and their caregivers are considered.
Prioritizing
these patient-centric
aspects
ensures
acceptance/
adherence and minimizes treatment-related challenges.
Kanji: Many factors influence pediatric dosage form design and
selection. To start, the inherent properties of the drug itself are clearly
influential, including taste/palatability and the physicochemical
properties of the required dose form. The choice and levels of
excipients must also be carefully considered to ensure safety and
mitigate the risk of adverse effects, especially in young children.
Patient-related factors may include broader acceptability criteria,
such as swallowability of solid oral dosage forms, and the container
Pharmaceutical Outsourcing | 28 | April/May/June 2024
Pharmaceutical Outsourcing Q2 2024

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