This document discusses physiological challenges in pediatric drug delivery and innovative delivery systems and devices. It begins by outlining the age categories in pediatrics and challenges including variable physiology, pharmacokinetics, and ensuring accurate dosing. Common challenges with absorption, distribution, and metabolism in pediatric patients are described. The document then discusses three major classifications of innovative delivery systems: oral, transdermal, and pulmonary. Several novel oral and transdermal delivery devices and formulations are presented, including thin films, microneedles, and needle-free injection devices. Aerosol delivery devices tailored for pediatric use like the Watchhaler and Funhaler are also summarized. The document concludes by discussing oral delivery of antiretroviral

1. PEDIATRIC DRUG DELIVERY
SYSTEM:PHYSIOLOGICAL CHALLENGES AND
DEVICES
Presented by-
Mr. Sangram M. Patil
M. Pharm
Department of Pharmaceutics
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2.  INTRODUCTION
 PHYSIOLOGICAL CHALLENGES
 CLASSIFICATION OF INNOVATIVE PEDIATRIC
DRUG DELIVERY SYSTEMS AND DEVICES
 REFERENCES
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3.  The pediatric population is divided, by age into six
categories.
Term Age
Pediatric 0-18yr
Premature <37 weeks
Neonate 1 day to 1 month
Infant 1 month to 1 year
Child 1 to 12 years
Adolescent 12 to 18 years
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4.  Administration of Pediatric medicines needs to be accurate
and to ensure the correct dose, the administration device
should be easy to use and acceptable.
 Patients in this population vary widely in physiologic,
pharmacokinetic ,pharmacodynamics, and physical
capabilities.
 These changes makes pediatric patient care extremely
challenging with respect to finding a correct drug pertaining
to patients medical condition, to identify appropriate
formulations convenient for administration.
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5. 1)Absorption :
 Early neonates (2 weeks) are in a state of achlorhydria where the
gastric acid production in stomach is absent. This may significantly
hamper the therapeutic efficacy of orally administered drugs which
requires acidic media for drug release and absorption.
 Altered gastric emptying in neonates is irregular, unpredictable and
prolonged.
 They have protracted rate of gastric emptying which results in
delayed absorption of medicament through intestines, which may
increase drug degradation due to prolonged contact with gastric
contents.
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6.  Pancreatic enzyme activity is initially low but develops gradually
and affects drugs bioavailability which depends on these
enzymes.
 Absorption via non-oral routes is different in pediatric patients
since their skin surface area is thrice that of adults relative to
weight, thereby increasing drug absorption applied topically.
Further the skin is more hydrated and thinner than adults with
increased hydration allowing deep drug penetration but may
result in increase the systemic absorption and toxicity.
 Neonates also have low concentrations of bile acids and lipase,
which may decrease the absorption of lipid-soluble drugs.
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7. 2)Distribution:
 Infants have high ratio of total body water than adults,
generating a large volume of distribution for hydrophilic drugs
and low volume of distribution for lipophilic drugs.
 Infants have decreased level of albumin, modified protein
binding characteristics, and increased competition for binding
endogenous substances.
 Tissue permeability, perfusion rate, tissue-drug binding are
major factors affecting drug distribution. Decrease in liver
volume, regional blood flow of liver reduces drug
biotransformation through hydrolysis, oxidation and reduction.
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8. 3)Metabolism and Elimination
 Drug metabolism is substantially slower in infants compared with
older children and adults.
 Less maturation of various pathways of metabolism within a
infant.
 Enzyme cytochrome P-450 (CYP450) present in the liver is
extensively involved in drug metabolism.
 The processes of glomerular filtration, tubular secretion, and
tubular reabsorption determine the efficiency of renal excretion.
These processes may take several weeks to 1 year after birth to
develop fully.
 Glomerular filtration rate is about 2–4 ml/min/1.73 m2 in term
infants.
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9. 1)Oral Drug Delivery Systems
2)Transdermal Drug Delivery Systems
3)Pulmonary Drug Delivery Systems
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10.  Oral delivery is the preferred route of administration in pediatric
patients because it is not invasive and carries a low risk of pain.
 Parents will generally feel comfortable with this delivery method,
leading to improved compliance for drugs administered via this
route.
 However, the oral route has several drawbacks for drug delivery in
neonates. Primarily, oral delivery is not an option when the
newborn is seriously ill or otherwise cannot swallow or tolerate
anything in his/her mouth.
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11. i) Medibottle:
It consists of a traditional baby bottle and an oral dispenser that
fits into the central part of the bottle. The dispenser contains
the required dose of which is to be inserted into the bottle filled
with milk or other drinks. On drinking the dispenser plunger
quickly moves down to produce a jet of medicine with every sip
of the milk or drink and is swallowed by the baby.
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12. ii)Pulp-Spoon:
It is developed for dosing dry medicaments. The drug in the
spoon is covered by a micro-perforated foil to improve the
stability of the product. The spoon is immersed in water for
several seconds, the cover peels off and the dose is administered
in form of a paste. This type of product is most suitable for
young children and offers convenience of unit dose and avoids
risk of spillage.
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13. XStraw is a drinking straw filled with pellets. The patient cannot
taste the tiny balls in the straw, and hardly feels them. He can
enjoy his favourite drink with the XStraw, while at the same time
taking the exact amount of medicine prescribed – without any
unpleasant taste.
New oral drug delivery device for pellets
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15.  Oral thin films also known as oral strips or patches are single
or multi-layer system of 2-10cm2 with thickness of 20-500µm.
 Films improve dosing accuracy compared to liquid
formulations with rapid onset of action, dose reduction,
enhanced drug efficacy and safety.
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16.  TDDS is an attractive alternative to oral and parenteral routes
and overcomes palatability, taste masking, gastrointestinal drug
degradation, first-pass metabolism, hepatotoxicity, pain on
injection, needle-stick injuries, prolong drug release, improve
bioavailability and enhance patient compliance.
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17.  A microneedle consists of hundreds of microfabricated
microneedles over a base substrate, which can pierce the stratum
corneum and create transient pathways to enable penetration and
delivery of drugs.
 Due to small needles the drug delivery by microneedle is
painless relative to hypodermic needle.
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18. Types of microneedle
The design and type of microneedle influences the drug delivery
mechanism.
i) Solid Microneedles:
They can be pressed against the skin to increase drug permeability
via transdermal patch or topical formulation.
ii)Biodegradable or water-soluble polymer based microneedles:
They have been fabricated for depot controlled release of drugs.
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19.  Needle-free devices deliver drugs and large molecules such as
insulin, vaccines, growth hormone and local anesthetics via both
subcutaneous and intramuscular routes.
 These devices can deliver liquid formulations under high
pressure through a very small orifice, which penetrates the skin.
 Needle-free devices are patient friendly as they eliminate the
fear of needles, providing easy handling and disposal of needles.
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21.  Aerosol therapy for children and patients with a poor
coordination is not a reliable application method, if
conventional hand held devices like MDIs or DPIs are
used. Especially for children, only an optimal flow rate
can lead to a satisfactory particle deposition within the
lung, because most aerosol devices are not developed
for children. The particle size produced by these devices
is too big for an efficient aerosol delivery to the
children's lungs.
 To make aerosol therapy more efficient, it is essential to
use a low inhalation flow rate during inspiration of the
aerosol in order to avoid most of the aerosol depositing
in the extra thoracic airways.
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22. Watchhaler is designed to be used in combination with metered
dose inhalers, for treatment of pulmonary conditions like asthma.
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23. 1)Filling:
The MDI canister is
put on the mouth piece
and is actuated.
2)Inhalation:
During inspiration, the
deflation of the balloon
can be seen.
3)Complete:
The totally deflated
balloon shows the
successful breathing
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24.  Continuous inhalation flow controlled by a mechanical valve
 Limitation of inhalation volume by a balloon
 High intra thoracic deposition Reproducible dosage
 Pure mechanical driven, no electronics
 Visual control of inhalation
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25.  which consists of a valve holding chamber with an internal
spinning disc and a whistle. The disc spins and the device
whistles when the child breathes normally encouraging them
to take the medication.
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26.  Simply Place the Funhaler mouthpiece or if using the mask,
place the mask over childs mouth & nose.
 The Funhalers unique internal Spinner & Whistle encourages
the child to breathe normally.
 Whilst the child is breathing through the Funhaler the parent
applies the correct medication dosage.
 The Child then enjoys the Fun sound of the whistle & watches
as Wally The Whale Spins during Inhalation & exhaltion.
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27.  Oral delivery of Antiretroviral drugs in infants through
breastfeeding.
 The two major reasons for use of antiretroviral drugs in
children is to prevent mother-to-child transmission of HIV
during perinatal period and to treat children already infected
with the virus.
 Many current medicines used for treatment of HIV are
available only in adult strengths, resulting in complications
regarding safe use and dose accuracy in infants. Thus there is
an urgent need for development of safe, effective, efficacious
and tolerable ARV drugs for treatment of HIV in pediatric
patients.
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28. Insert containing active agent
Modified silicone nipple
shield
Lip to hold insert
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29.  Simple single-use disposable low cost device with correct
dosing
 Easy application
 Dry drug formulation offers improved stability over liquid
formulations
 Milk may mask taste of oral administered drugs improving
acceptability
 No sterilization required
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30.  Felipe L. Lopez, Terry B. Ernest et.al., (2015), Formulation Approaches
To Pediatric Oral Drug Delivery: Benefits And Limitations of Current
Platforms ,12(11):1-14.
 Ankita Mistry ,Sonali Kapse (2015), Innovative Pediatric Drug Delivery
Systems ,Journal of Harmonized Research In Pharmacy 4(2):117-130.
 Verica Ivanovska et.al.,(2014), Pediatric Drug Formulations: A Review Of
Challenges and Progress, Pediatrics 134(2): 361-371.
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