Journal of Pharmaceutical Sciences 108 (2019) 1335-1365

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Journal of Pharmaceutical Sciences

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Review

Pediatric Oral Formulations: An Updated Review of Commercially

Available Pediatric Oral Formulations Since 2007
Robert G. Strickley*

a r t i c l e i n f o a b s t r a c t

Article history: Oral pediatric formulations are either ready-to-use or require manipulation and multiuse or single-use.
Received 6 August 2018 Strong encouragement for preservative-free pediatric formulations has resulted in fewer multiuse so-
Revised 23 October 2018 lutions or suspensions in favor of single-use solid oral dosage forms. This updated review covering new
Accepted 7 November 2018
pediatric formulations marketed in the United States of America, Europe, and Japan spanning the years
Available online 14 November 2018
2007 to mid-2018 identified 16 types of pediatric oral formulations of which 7 are ready-to-use and 9
require manipulation, and 51 total new pediatric oral formulations of which 21 are ready-to-use and 30
Keywords:
formulation require manipulation. Ready-to-use formulations include oral solution, oral suspension, oral soluble film,
oral drug delivery tablet, scored tablets, orally disintegrating tablet, chewable tablet, and mini-tablets. Formulations
pediatric requiring manipulation include sprinkle capsule, powder for oral solution, powder for oral suspension,
excipient(s)
granules for oral suspension, oral powder, oral granules, tablet, dispersible tablet, dispersible scored
tablet, tablet for oral suspension, and mini-tablets (oral granules). Significant advances in packaging
technology include filling mini-tablets, granules, or powders into sachets, stick packets, blisters, and 2-
piece capsules. The future of pediatric oral formulations will increasingly be with user-friendly, preser-
vative-free, taste-masked formulations including multiparticulate single-use solid dosage forms
including mini-tablets, orally disintegrating tablets, and sprinkle capsules with or without a specialized
package configuration.
© 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Introduction and Japan that began commercialization starting in 2007 to the

Pediatric formulations continue to be scientifically challenging
and there have been many advances since the author’s previous
review published in 2008.1 The most significant advance has been
the strong encouragement for preservative-free pediatric formu-
lations that has resulted in fewer multiuse solutions or suspensions
in favor of single-use solid oral dosage forms including mini-tablets
(also known as granules), orally disintegrating tablets (ODTs),
single-use powder for oral suspension or oral solution, oral soluble
films and multiple multiparticulates including sprinkle capsules,
oral powders, oral granules, and manipulated mini-tablets. A
consequence of the trend to single-use solid oral dosage forms has
also resulted in significant advances in packaging technology in
powder-filling or granule-filling into sachets, stick packets, blisters,
and capsules.
This updated review attempts to capture the newly approved
oral pediatric drug products in the United State of America, Europe,
Conflict of interest: The authors have no conflict of interest to disclose.
* Correspondence to: Robert G. Strickley (Telephone: þ1-650-278-6871).
E-mail address: strickleyrobert@gmail.com (R.G. Strickley).
present (mid-2018). This review does not cover generics, over-the-
counter products, or parenterals. Although many new oral pediatric
drug products were identified, and the author attempted to be
comprehensive, there will be commercial products that were not
identified, but this review provides the reader with an update in the
trends and listing of newly approved oral pediatric formulations.
Many of the recent advancements in pediatric formulations
were spurred initially by far-sighted government regulation in-
centives encouraging development of pediatric formulations. Now
the development of pediatric formulation(s) is standard practice
and is normally conducted when the new chemical entity is in
phase 2 clinical trials. Pediatric formulations in recent years have
been an active area of international interest including a theme issue
in AAPS PharmSciTech2 in 2017, a book3 in 2014, an Arden Con-
ference4 in 2014, a review in 2014 on challenges and progress,5 and
a review in 2013 of prescription and over-the-counter pediatric
medications for allergic rhinitis, cough, and cold.6 A European
perspective7 discussed a focus on mini-tablets, orodispersible films,
excipient safety, and adequate user instructions (along with useful
references). There has been more attention to primary packaging8
and delivery devices.9

https://doi.org/10.1016/j.xphs.2018.11.013
0022-3549/© 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
1336 R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365

Pediatric oral formulations have some similarity to geriatric

formulations for older adults because both populations have similar
challenges including swallowing.10-12 Some key considerations in
the development of these formulations include efficacy and ease of
use, safety, and patient access.11,13 Many pediatric oral formulations
require manipulation before use, and authorized instructions are
provided, but in practice, there is sometimes nonauthorized com-
pounding or manipulation of a drug product.14
It is the author’s opinion that mini-tablets will be the future of
pediatric oral formulations. Mini-tablets range in diameter of 2-4
mm and are manufactured using multitip tablet compression
tooling with 2-mm tooling shown in Figure 1 and 2-mm mini-
tablets shown in Figure 2. As of this writing, mini-tablets are not
administered individually but are packaged and administered with
20 mini-tablets in sachet. Mini-tablets are currently called gran-
ules and may bring into question the definition of a tablet. There
has been significant amount of research to determine at what age a
child can safely be administered an individual mini-tablet, and for a
placebo 2-mm diameter uncoated16 or coated17 mini-tablet, that
age has been determined to be as young a 2-28 days by observa-
tions of the child and feedback from the parent of caregiver, and
indeed mini-tablets were determined to be preferred over an oral
suspension and oral powder. Another study showed that placebo 4-
mm diameter uncoated mini-tablets can be administered to chil-
dren from 1 year of age.18 Another study showed that children from
2 years of age were able to be administered 5 to 10 placebo mini-
tablets on a spoon or with fruit jelly soft food.19 A recent clinical
study showed that administration of 25 uncoated mini-tablets (2
mm in diameter and height) is well-tolerated, feasible, and safe in
children aged as young as 6 months and was superior to the
equivalent dose of syrup.20
The literature on mini-tablets goes back to 1989 with an article
using 3-mm diameter coated mini-tablets of a mass of 20 mg for
the controlled release of theophylline using 20 mini-tablets in a
capsule.21 The literature on mini-tablets appears to have increased
starting in 2009 with a publication on the ability of children 2 to 6
years of age to swallow a 3-mm uncoated placebo mini-tablet as a
new modality to deliver medicines to preschool-aged children.22
The literature on mini-tablets includes, in chronological order,
orally disintegrating mini-tablets,23 treatment of infants aged 6-30
months with cystic fibrosis with 2-mm mini-tablets,24 delayed
release 2- to 4-mm mini-tablets,25 levamisole filmecoated 5- to 8- Figure 2. (a) Mini-tablets of 2-mm diameter on a U.S. penny. (b) Multiple mini-tablets
mm mini-tablets,26 orally disintegrating films and mini-tablets,27 of 2-mm diameter and height in relation to a $1 U.S. coin.15
the acceptability of 2-mm uncoated mini-tablets in neonates of
age 2-28 days compared to a syrup,15 a review article28 in 2014, and Age-appropriate considerations are important for pediatric oral
understanding the manufacturing factors that control the quality of formulations, and Table 1 lists the pediatric age range, approximate
the mini-tablet compression process.29 mass, classification, current dosage forms, and proposed dosage
forms.
Soft foods are often used to mix pediatric oral formulations, and
a recent regulatory Food and Drug Administration draft guidance
was published online.30 The draft guidance included a table, which
is reproduced in Table 2, of a listing of soft food with their pH
values, which are all slightly to moderately acidic with a pH range of
2.3-7.0.
This updated review spanning the years 2007 to mid-2018
identified 16 types of pediatric oral formulations of which 7 are
ready-to-use and 9 require manipulation and 51 total new pediatric
oral formulations of which 21 are ready-to-use and 30 require
manipulation. The bar chart in Figure 3 shows the occurrences for
the various types of pediatric oral formulations identified in this
updated review: 12 multiparticulates (6 sprinkle capsules, 2 oral
powders, 3 oral granules, and 1 manipulated mini-tablet known as
oral granules), 7 oral solutions, 6 granules for oral suspension, 5 oral
suspensions, 5 tablets ready-to-use, 3 powders for oral solution, 2
Figure 1. Multitip 2-mm tooling for manufacture of mini-tablets. manipulated tablets, 2 scored tablets, 2 powder for oral suspension,
 R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365 1337

Table 1
Age-Appropriate Pediatric Oral Formulations: Current and Proposed

Age Mass (kg) Classification Age-Appropriate Dosage Forms, Current Age-Appropriate Dosage Forms, Proposed

<3 Preterm infant Nasogastric tube using solution or suspension Nasogastric tube using tablets for oral
(ready-to-use or powder or granules for suspension
constitution)
0-28 d 3-5 Term new born infants Solution or suspension (ready-to-use or powder Tablets for oral suspension
or granules for constitution)
1 mo-2 y 5-10 Infants and Toddlers Solution, suspension, mini-tablets, ODT Mini-tablet(s)
2-6 y 10-25 Children (preschool) Mini-tablets, ODT, sprinkle powder, oral
powder, oral granules
6-12 y <25 Children (school) Chewable tablets, ODT Chewable tablets, ODT, mini-tablets
12-18 y >25 Adolescent Small tablets, capsules Small tablets, capsules, mini-tablets
>18 y >40 Adult Tablets, capsules Tablets, capsules, mini-tablets

and 1 each of mini-tablet ready-to-use, oral soluble film, ODT,
chewable tablet, dispersible tablet, tablet for oral suspension, and
concentrated oral suspension. The decision on the type of pediatric
oral formulation to develop depends on multiple factors and
properties of the drug substance, and Figure 4 is a suggested
decision-making flow-chart with yes and no decision points start-
ing with the decision to develop a preserved or preservative-free
formulation, then upon drug substance properties of acceptable
taste-masking, then water soluble, and then chemically stable. The
left half of Figure 4 are preserved multiuse or single-use formula-
tions, whereas the right half are preservative-free single-use for-
mulations. Another decision tree based on taste masking
approaches to age-appropriate formulations was intended to
be a rational and practical proposal that may be applied during
development.31
Some alternative and innovative oral pediatric formulations
include a drinking straw and an XStraw®, as shown in Figure 5. The
Clarosip® drinking straw from IP technology by Grünenthal GmbH
was introduced in 2006, but discontinued in 2009, and it was a
drinking straw that contained a premeasured dose of the antibiotic
clarithromycin in a formulation of coated taste-masked granules
and was administered with a pulp-free beverage of the patient’s
choice, cold or hot. The XStraw® appears to be in development and
is a potential new product from the company Dose Sipping
Table 2
Soft Foods and Their pH Values From an FDA Draft Guidance Document25
Soft Food
Technology (DS Technology) that is a subsidiary of the company
Harro Ho € fliger. The XStraw® is a drinking straw filled with exactly
the required dosage in the form of pellets and is made of poly-
propylene and an air-tight packaging in an aluminum blister; thus,
special storage conditions are not required.32
Some innovative delivery devices are under development
including a mini-tablet dispenser and a multiparticulate dispenser.
The sMTS is a smart mini-tablet dispenser with a rotation compo-
nent for controlled release of tablets (Fig. 6).33 Sympfiny™ is an
innovative system for dosing and dispensing multiparticulate, dry
powder, and microsphere drug formulations for oral delivery
(Fig. 7).34 Designed with the entire supply chain in mind, the sys-
tem Sympfiny™ fits common bottle sizes and can be prefilled or
filled at a pharmacy. The internal valve and bottle cap protect the
drug through storage and use. The reusable syringe comes in 2 sizes
and has selectable dose settings.
Overall, the trend in pediatric oral formulations is toward flex-
ible solid dosage forms as recommended in a 2008 World Health
Organization report35 and another World Health Organization
report from 2011 and 2012.36,37
Methodology
New oral pediatric formulations were identified at their time of
approval by daily news letters from APhA’s Pharmacy Today
(PTdaily@aphanet.org) as a main source of daily information. The
prescribing information for that specific drug product is the source
of the formulation information. The pictures are images from the
pH Range
internet after a search for the drug product.

Apples (puree) 3.34-3.90

Applesauce 3.35-4.00 Ready-to-Use Oral Formulations
Baby food, unstrained 5.95-6.05
Bananas (puree) 4.5-5.2 Ready-to-use pediatric oral formulations are available as many
Buttermilk 4.41-4.83
types including solution, suspension, oral soluble film, and multiple
Carrots (puree) 5.88-6.40
Chocolate pudding 5.5-6.0 types of tablets including small tablet, scored tablet, ODT, chewable
Coconut milk 6.1-7.0 tablet, and mini-tablets. Table 3 is a listing of identified ready-to-
Cranberry juice 2.30-2.52 use pediatric oral formulations that were commercialized be-
Fruit jellies 3.0-3.5 tween the years 2007 and mid-2018.
Grapefruit juice 2.90-3.25
Honey 3.7-4.2
Infant formula 5.7-6.0 Oral Solutions
Maple syrup 4.6-5.15
Milk 6.4-6.8
Oral solutions were a standard multiuse type of aqueous-based
Orange juice 3.30-4.19
Orange marmalade 3.00-3.33 pediatric formulation until the recent trend toward preservative-
Peanut butter 6.28 free formulations.
Pineapple juice 3.3-3.6
Rice pudding 4-5
Soybean milk 7 Organic-Based Oral Solution
Strawberries 3.0-3.9
Strawberry jam 3.3-3.4 Epidiolex® (cannabidiol) oral solution from Greenwich Bio-
Yogurt 4.4-5.0 sciences, Inc., was approved in 2017 for the treatment of seizures
associated with Lennox-Gastaut syndrome (LGS) or Dravet
1338 R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365

12
10
8 ManipulaƟon Required
6
4
Ready-to-Use
2
0

Figure 3. Bar chart of the occurrence in this updated review of oral pediatric formulations from 2007 to mid-2018. Notes that multiparticulates include sprinkle capsules, oral
powders, oral granules, and mini-tablet for manipulation.

syndrome with a dose of 2.5-5 mg/kg twice daily using a dose
volume of 0.025-0.50 mL/kg of a preservative-free organic-based
100 mg/mL formulation containing ethanol, sesame seed oil,
strawberry flavor, and sucralose.
Aqueous-Based Oral Solutions
Epaned® (enalapril maleate) oral solution from Silvergate
Pharmaceuticals, Inc., was approved in 2017 as a ready-to-use
replacement to the kit that required manipulation and included a
bottle of powder and a bottle of Ora-Sweet diluent. Epaned® is
indicated for the treatment of hypertension with a dose of 0.08 mg/
kg up to 5 mg once daily using a dose volume of 0.08 mL/kg up to 5
mL of a 1 mg/mL formulation containing citric acid, mixed berry
flavor, sodium benzoate, sodium citrate, sucralose and water.
Desitrend® (levetiracetam) oral solution from Desitin Phar-
maceuticals GmbH was approved in 2011 for the treatment of
seizures with a dose of 10-30 mg/kg twice daily using a dose
volume of 0.1-0.3 mL/kg of a 100 mg/mL formulation containing
sodium citrate, citric acid, methylparaben (2.7 mg/mL),
propylparaben (0.3 mg/mL), ammonium glycyrrhizate, glycerol,
maltitol liquid 300 mg/mL, acesulfame potassium, grapefruit fla-
vor, and water.
Buccolam® (midazolam) oral solution from Shire Pharmaceuti-
cals and ViroPharma was approved in 2011 for the treatment of
seizures and is available in prefilled age-specific syringes with unit
doses of 2.5 mg, 5 mg, 7.5 mg, or 10 mg in volumes of 0.5 mL, 1 mL,
1.5 mL, or 2 mL of a 5 mg/mL preservative-free formulation con-
taining sodium chloride and water with pH 3.3 (HCl or NaOH).
Buccolam® oral solution is oromucosal midazolam that provides for
convenient buccal (i.e., via the cavity between the cheek and gum)
delivery. Buccolam® (midazolam) oral solution appears to be only
available in the United Kingdom, European Union, and European
Economic Area.
Zofran® (ondansetron HCl) oral solution from GlaxoSmithKline
was approved in 2013 for the treatment of nausea with a thrice-
daily dose of 4 mg for age 4-11 years or 8 mg for age 12-17 years
using dose volumes of 5 mL or 10 mL of a 0.8 mg/mL formulation
containing citric acid, sodium benzoate, sodium citrate, sorbitol,
strawberry flavor, and water.

Figure 4. Suggested decision-making flow-chart in the choice of a pediatric oral formulation.

 R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365 1339

Figure 5. Alternative pediatric oral formulations. (a) Drinking straw was introduced in 2006 but discontinued in 2009. (b-d) XStraw® is in development.31

Hemangeol™ (propranolol HCl) oral solution from Pierre Fabre using a dose volume of 0.0625-0.125 mL/kg of a 20 mg/mL
Pharmaceuticals, Inc., was approved in 2014 for the treatment of formulation containing xanthan gum, aspartame, raspberry juice,
proliferating infantile hemangioma requiring systemic therapy sucrose, methylparaben, propylparaben, and water.
with a dose 0.6-1.7 mg/kg twice daily using a dose volume of 0.15- Noxafil® (posaconazole) from Merck was approved in 2006 as an
0.4 mL/kg of a 4.28 mg/mL (equivalent to 3.75 mg/mL propranolol) antifungal with a dose of 100-400 mg using a dose volume 2.5-10
containing strawberry and vanilla flavorings, hydroxyethyl cellu- mL of a 40 mg/mL formulation containing polysorbate 80, sime-
lose, saccharin sodium, citric acid, and water. If necessary, the thicone, sodium benzoate, sodium citrate, citric acid, glycerin,
product may be diluted in a small quantity of milk or fruit juice, xanthan gum, liquid glucose, titanium dioxide, artificial cherry
given in a baby’s bottle. flavor, and water. Use the provided plastic calibrated spoon to
Prexxartan™ (valsartan) oral solution from Medicure Pharma, measure and administer the dose.
Inc., was approved in 2017 as an ACE inhibitor for the treatment of
hypertension with a twice-daily dose of 0.65-1.35 mg/kg (up to 40-
160 mg) using a dose volume 0.16-0.34 mL/kg (up to 10-40 mL) of a
4 mg/mL formulation containing grape flavor, methylparaben,
poloxamer 188, potassium sorbate, propylene glycol, sodium cit-
rate, sucralose, and water. Diovan (valsartan) oral solution from
Novartis is available in Europe at a concentration of 3 mg/mL.

Oral Suspensions

Onfi® (clobazam) oral suspension from Lundbeck was approved

in 2011 for the treatment of seizure only with LGS with a dose of 5-
40 mg using a dose volume of 2-16 mL of a 2.5 mg/mL formulation
containing magnesium aluminum silicate, xanthan gum, citric acid,
disodium phosphate, simethicone emulsion, polysorbate 80,
methylparaben, propylparaben, PG, sucralose, maltitol solution,
berry flavor, and water.
Felbatol® (felbamate) oral suspension from Meda Pharmaceu-
ticals was approved in 2011 also for the treatment of seizure only
with LGS with a 3 or 4 timesedaily dose of 15-45 mg/kg/d using a
dose volume of 0.031-0.12 mL/kg of a 120 mg/mL formulation
containing sorbitol, glycerin, microcrystalline cellulose,
carboxymethyl-cellulose sodium, simethicone, polysorbate 80,
methylparaben, saccharin sodium, propylparaben, FD&C Yellow No.
6, FD&C Red No. 40, flavorings, and water.
Purixan™ (mercaptopurine) oral suspension from Rare Disease
Therapeutics, Inc., was approved in 2014 for the treatment of acute Figure 6. The sMTS is a smart mini-tablet dispenser with a rotation component for
lymphoblastic leukemia with a once-daily dose of 1.5-2.5 mg/kg controlled release of tablets.32
1340 R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365
Figure 7. (a and b) Sympfiny™ is an innovative system for dosing and dispensing multiparticulates, dry powder, and microsphere, drug formulations for oral delivery.33
Banzel® (rufinamide) oral suspension from Eisai was approved
in 2015 also for the treatment of seizure only with LGS with a twice-
daily dose of 5-22.5 mg/kg up to 1600 mg using a dose volume
0.125-0.56 mL/kg up to 40 mL of a 40 mg/mL formulation con-
taining microcrystalline cellulose, carboxymethylcellulose sodium,
hydroxyethyl cellulose, citric acid, simethicone emulsion, polox-
amer 188, methylparaben, propylparaben, propylene glycol, po-
tassium sorbate, sorbitol solution 70% (~30% water), and orange
flavor.
Oral Soluble Films
Zuplenz® (ondansetron) oral soluble film from Strativa Pharma-
ceuticals, the proprietary products division of Par Pharmaceutical,
was approved in 2010 for the prevention of nausea- and vomiting-
associated chemotherapy, radiotherapy, or postoperative nausea
with unit doses of 4 mg or 8 mg for a dose of one 4-mg film 3 times a
day of a preservative-free formulation containing butylated hydrox-
ytoluene, calcium carbonate, colloidal silicon dioxide, erythritol,
hydroxypropyl methylcellulose, monoammonium glycyrrhizinate,
peppermint flavor, polyethylene oxide, sodium bicarbonate, sucra-
lose, titanium dioxide, and xanthan gum. The film’s surface areas are
0.55 in2 and 1.09 in2. The film is applied on top of the tongue where it
will dissolve in 4 to 20 s and then is swallowed with saliva and does
not require water to aid dissolution or swallowing. In 2015, Galena
Biopharma, Inc., announced the launch for Zuplenz® (ondansetron)
oral soluble film in the United States.
Tablets, Ready-to-Use
Multiple types of ready-to-use tablets are available as pediatric
oral formulations including small tablets, scored tablets, ODTs,
chewable tablets, and mini-tablets.
Tablets
Tivicay® (dolutegravir sodium) from ViiV Healthcare was
approved in 2013 as an antiviral with a once-daily dose of 35 mg or
50 mg using tablets of unit doses of 10 mg, 25 mg, or 50 mg in a
preservative-free formulation containing mannitol, microcrystal-
line cellulose, povidone, sodium starch glycolate, and sodium
stearyl fumarate. The Tivicay® tablets are administered whole.
Aptiom® (eslicarbazepine acetate, a prodrug) from Sunovion
Pharmaceuticals, Inc., was approved in 2013 for the treatment of
partial-onset seizures with a once-daily dose of 200-1200 mg using
tablets of unit doses of 200 mg, 400 mg, 600 mg, or 800 mg, all of
which are scored except the 400 mg, in a preservative-free
formulation containing croscarmellose sodium, magnesium stea-
rate, and povidone. The Aptiom® tablets are administered whole or
can be crushed.
Viread® (tenofovir disoproxil fumarate) low-dose tablets (150
mg, 200 mg, and 250 mg) from Gilead Sciences were approved in
2017 as an antiviral with a daily dose determined by body mass
with 17-22 kg one 150-mg tablet, 22-28 kg one 200-mg tablet, 28-
35 kg one 250-mg tablet, and >35 kg one 300-mg adult tablet in a
preservative-free formulation containing croscarmellose sodium,
lactose monohydrate, magnesium stearate, microcrystalline cellu-
lose, and pregelatinized starch. The Viread® tablets are adminis-
tered whole and should not be crushed. See Viread® Oral Powder
for a measurable pediatric formulation.
Orkambi® tablets is a fixed-dose combination of lumacaftor and
ivacaftor (100 mg and 125 mg, or 200 mg and 125 mg) from Vertex
and approved in 2015 for the treatment of cystic fibrosis with a twice-
daily dose determined by age of 6-11 years a dose of two 100 mg/125
mg tablets, and 12 years a dose of two 200 mg/125 mg tablets in a
preservative-free formulation containing microcrystalline cellulose,
croscarmellose sodium, hypromellose acetate succinate, magnesium
stearate, povidone, and sodium lauryl sulfate. See Orkambi® oral
granules for ages <6 years.
Scored Tablets
Banzel® (rufinamide) scored tablets from Eisai were approved in
2009 for the treatment of seizure only with LGS with a twice-daily
dose of 5-22.5 mg/kg up to 1600 mg using scored tablets of unit
doses 200 mg or 400 mg of a preservative-free formulation con-
taining colloidal silicon dioxide, corn starch, croscarmellose so-
dium, hypromellose, lactose monohydrate, magnesium stearate,
and microcrystalline cellulose. The Banzel® tablets can be swal-
lowed whole, cut in half, or crushed.
Orally Disintegrating Tablets
Zofran ODT® (ondansetron, free base) ODTs from Glax-
oSmithKline were approved in 2013 for the treatment of nausea
with a thrice-daily dose of 4 mg for age 4-11 years or 8 mg for age
12-17 years using unit dose ODT of 4 mg or 8 mg of a freeze-dried
Zydis® formulation containing aspartame, gelatin, mannitol,
methylparaben, propylparaben, and strawberry flavor. The Zofran
ODT® is administered orally whole and rapidly disintegrates on the
tongue and does not require water to aid dissolution or swallowing.
Chewable Tablets
Isentress® (raltegravir) chewable tablets from Merck were
approved in 2014 as an antiviral with a twice-daily dose of 75 mg,
Table 3
Pediatric Formulations Marketed since 2007: Ready-To-Use

Drug Name/Marketed Name/Year Marketed Formulation/ Active in Formulation Dose Inactive in Formulation (as Preparation Company/Indication
approved/Country Storage/Package Listed in Package Insert)

Cannabidiol/Epidiolex®/2017/EU/USA Oral Solution/room 100 mg/mL 2.5-5 mg/kg (b)i.d. dose Ethanol None Greenwich Biosciences,
temperature/bottle, volume: 0.025-0.50 Sesame seed oil Inc./Treatment of
100 mL mL/kg Strawberry flavor seizures associated with
Sucralose preservative-free Lennox-Gastaut
syndrome or Dravet
syndrome
Clobazam/Onfi®/2011/USA Oral suspension/room 2.5 mg/mL 5 mg-40 mg dose Magnesium aluminum silicate None Lundbeck/anti-seizure only
Epaclob® in France, Ireland, Germany temperature/bottle volume: 2-16 mL Xanthan gum with Lennox-Gastaut
and Italy; and Silocalm® in Denmark, with, bottle adapter, Citric acid syndrome (LGS)
Spain and Iceland by Martindale 2 plastic 10-mL Disodium phosphate
Pharma syringes Simethicone emulsion
Polysorbate 80
Methylparaben
Propylparaben

R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365

PG
Sucralose
Maltitol solution
Berry flavor
Water

Dolutegravir sodium/Tivicay®/2013/EU/ Tablet/room 10 mg, 25 mg, or 50 mg 35 mg qd Mannitol None ViiV Healthcare,

USA/Japan temperature/bottles 30-40 kg Microcrystalline cellulose GlaxoSmithKline/
50 mg qd at least 40 kg Povidone Antiviral
Sodium starch glycolate
Sodium stearyl fumarate
preservative-free
Enalapril/Epaned®/2017/USA Oral solution/room 1 mg/mL 0.08 mg/kg up to 5 mg Citric acid None Silvergate Pharmaceuticals,
temperature/bottle, QD Mixed berry flavor Inc./Hypertension
150 mL dose volume: 0.08 mL/ Sodium benzoate
kg Sodium citrate
Sucralose
Water
Eslicarbazepine acetate (prodrug)/ Tablets/room 200 mg, 400 mg, 600 mg, 200-1200 mg qd Croscarmellose sodium None or can be crushed Sunovion Pharmaceuticals,
Aptiom®/2013/EU/USA Zebinix in temperature/bottle 800 mg all are scored Magnesium stearate Inc./treatment of partial-
Europe by Eisai tablets, except the 400 Povidone preservative-free onset seizures
mg
(continued on next page)

1341
Table 3 (continued )

1342
Drug Name/Marketed Name/Year Marketed Formulation/ Active in Formulation Dose Inactive in Formulation (as Preparation Company/Indication
approved/Country Storage/Package Listed in Package Insert)

Felbamate/Felbatol®/2011/USA Oral suspension/room 120 mg/mL 15-45 mg/kg/d t.i.d or Sorbitol None Meda Pharmaceuticals/
temperature/bottles, q.i.d dose volume: Glycerin Antiseizure only with
8 oz. and 32 oz. 0.031-0.12 mL/kg Microcrystalline cellulose Lennox-Gastaut
Carboxymethylcellulose syndrome (LGS)

R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365

sodium
Simethicone
Polysorbate 80
Methylparaben
Saccharin sodium
Propylparaben
FD&C Yellow No. 6
FD&C Red No. 40
Flavorings
Water
Levetiracetam/Desitrend®/2011/EU Oral solution/room 100 mg/mL 10 mg/kg - 30 mg/kg (b) Sodium citrate None Desitin Pharmaceuticals
temperature/glass i.d. dose volume: 0.1- Citric acid GmbH/Antiepileptic,
bottle, 300 mL, and a 0.3 mL/kg Methylparaben 2.7 mg/mL treat seizures in epilepsy
1-mL oral syringe, Oral solution for infants Propylparaben 0.3 mg/mL
graduated every 0.05 and children under Ammonium glycyrrhizate
mL the age of 6 y Glycerol
Maltitol liquid 300 mg/mL
Acesulfame potassium
Grapefruit flavor
Water
Levetiracetam/Desitin®/2011/EU Mini-tablets/room 250 mg, 500 mg, or 1000 10 mg/kg - 30 mg/kg (b) Povidone K30 None, or coated Desitin Pharmaceuticals
temperature/stick mg per packet mini- i.d. Microcrystalline cellulose granules may also be GmbH/Antiepileptic,
packets tablets are 2 mm in Mini-tablets for Silica colloidal anhydrous suspended by treat seizures in epilepsy
diameter with 5 mg children >6 y Magnesium stearate shaking for a
levetiracetam per mini- Poly(vinyl alcohol) minimum of 2 min in
tablet Titanium dioxide at least 10 mL of
PEG 3350 water and
Talc administered via a
preservative-free feeding tube that
should be rinsed
twice with 10 mL of
water each,
immediately after
administration

Lumacaftor and Ivacaftor/Orkambi®/
2015/USA
R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365
Tablets/RT/blister Lumacaftor 100 mg and Age 6 through 11 y: 2 Microcrystalline cellulose None Vertex/Treatment of cystic
ivacaftor 125 mg or tablets (each Croscarmellose sodium fibrosis in patients age 2
lumacaftor 200 mg and containing Hypromellose acetate succinate y and older who have 2
ivacaftor 125 mg lumacaftor 100 mg/ Magnesium stearate copies of the F508del
ivacaftor 125 mg) Povidone mutation (F508del/
Age 12 y and older: 2 Sodium lauryl sulfate F508del) in their CFTR
tablets (each preservative-free gene
containing
lumacaftor 200 mg/
ivacaftor 125 mg)
Taken orally every 12 h
with fat-containing
food.

Mercaptopurine/Purixan™/2014/USA Oral suspension/room 20 mg/mL 1.5-2.5 mg/kg qd dose Xanthan gum None Rare disease therapeutics,
temperature/bottle, volume: 0.0625- Aspartame Inc./treatment of acute
100 mL 0.125 mL/kg Raspberry juice lymphoblastic leukemia
Sucrose (ALL)
Methylparaben
(continued on next page)

1343
Table 3 (continued )

1344
Drug Name/Marketed Name/Year Marketed Formulation/ Active in Formulation Dose Inactive in Formulation (as Preparation Company/Indication
approved/Country Storage/Package Listed in Package Insert)

®
Midazolam/Buccolam /2011/UK,
European Union and The European
Economic Area
Midazolam has odor
Propylparaben
Water
Oral solution/room 5 mg/mL 2.5 mg, 5 mg, 7.5 mg or Sodium chloride Nonedprefilled syringe Shire Pharmaceuticals
temperature, do not 10 mg dose volume: Sodium hydroxide Buccal administration Limited and ViroPharma/
refrigerate or freeze/ 0.5 mL, 1 mL, 1.5 mL, Hydrochloric acid Treatment of prolonged,
prefilled syringe 2 mL Water pH ¼ 2.9-3.7 acute, convulsive
preservative-free seizures in infants,
toddlers, children and
adolescents (from 3 mo
to <18 y).

R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365

Ondansetron/Zuplenz®/2010/USA
European Markets under the brand
Setofilm®
Oral soluble film/room 4 mg and 8 mg Pediatric patients 4 y Butylated hydroxytoluene
temperature/packets Dimensions: 0.55 in2 and through 11 y of age Calcium carbonate
of 10 per box 1.09 in2 One 4 mg film 3 times a Colloidal silicon dioxide
d Erythritol
Hydroxypropyl methylcellulose
Monoammonium
glycyrrhizinate
Peppermint flavor
Polyethylene oxide
Sodium bicarbonate
Sucralose
Titanium dioxide
Xanthan gum preservative-free
None Strativa Pharmaceuticals,
Applied on top of the the proprietary products
tongue where it will division of Par
dissolve in 4 to 20 s Pharmaceutical (In 2015
and then is Galena Biopharma)/
swallowed with prevention of nausea and
saliva, does not vomiting-associated
require water to aid chemotherapy,
dissolution or radiotherapy, or
swallowing postoperative nausea
Ondansetron HCl in oral solution, free 1. Oral Solution, 2. (1) Age 4-11: 4 mg t.i.d. (1) Oral solution: (1) GlaxoSmithKline/
base in orally disintegrating tablets/ Orally Disintegrating 4 mg/5 mL (0.8 mg/mL) dose volume: 5 mL None prevention of nausea
Zofran® and Zofran ODT®/2013/EU, Tablets/1. 15 C-30 C, (2) Age 12-17: 8 mg t.i.d. Citric acid (2)
USA 2. 2 C-30 C/1. Bottle, 4 mg or 8 mg dose volume: 10 mL Sodium benzoate None, rapidly
50 mL, 2. Blisters Sodium citrate disintegrates on the
(pictured) Sorbitol tongue and does not
Strawberry flavor require water to aid
Water dissolution or
swallowing
(2) ODT (freeze-dried, Zydis®):

Aspartame
Gelatin
Mannitol
Methylparaben
Propylparaben Strawberry
flavor

R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365

Posaconazole/Noxafil®/2006/EU, USA Oral suspension/Room 40 mg/mL 100 mg-400 mg Polysorbate 80 None Merck/Antifungal
temperature/Bottle, Ages 13-17 y Simethicone Use the provided plastic
105 mL, supplied After a full meal Sodium benzoate calibrated spoon to
with a plastic dosing Dose volume: 2.5-10 Sodium citrate measure and
spoon calibrated for mL Citric acid administer the dose
measuring 2.5 mL Glycerin
and 5 mL. Xanthan gum
Liquid glucose
Titanium dioxide
Artificial cherry flavor
Water
(continued on next page)

1345
Table 3 (continued )

1346
Drug Name/Marketed Name/Year Marketed Formulation/ Active in Formulation Dose Inactive in Formulation (as Preparation Company/Indication
approved/Country Storage/Package Listed in Package Insert)

R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365

Propranolol HCl/Hemangeol™/2014/ Oral solution/Room 4.28 mg/mL (equivalent to 0.6 mg/kg-1.7 mg/kg Strawberry and vanilla None Pierre Fabre
USA temperature, do not 3.75 mg/mL propranolol) b.i.d. flavorings If necessary, the Pharmaceuticals, Inc./
freeze. dose volume: 0.15-0.4 Hydroxyethyl cellulose product may be Proliferating infantile
The product can be kept mL/kg Saccharin sodium diluted in a small hemangioma requiring
for 2 mo after first Citric acid quantity of milk or systemic therapy.
opening./Bottle, 120 Water fruit juice, given in a
mL preservative-free baby’s bottle.
Raltegravir/Isentress®/2014/EU, USA Chewable tablets/Room 25 mg unscored or 100 mg 75 mg, 100 mg or 150 Ammonium hydroxide None Merck/Antiviral
temperature/Bottle scored (pictured) mg (b)i.d. Crospovidone
with desiccant 75 mg: three 25 mg Ethylcellulose 20 cP
100 mg: one 100 mg Fructose
150 mg: 1 and half 100 Hydroxypropyl cellulose
mg, 1 scored into Hypromellose 2910/6cP
equal halves Magnesium stearate
Mannitol
Medium chain triglycerides
Monoammonium
glycyrrhizinate
Natural flavors (orange, banana,
with aspartame)
Oleic acid
PEG 400
Saccharin sodium
Sodium citrate
Sodium stearyl fumarate
Sorbitol
Sucralose
 Yellow iron oxide
preservative-free
100 mg scored

Rufinamide/Banzel®/2009 (tablet) (1) (1) 5-22.5 mg/kg up to (1) Tablets: (1) Eisai/treatment of seizures
2015 (suspension)/USA Tablet Scored Tablets: 200 mg, 400 mg 1600 mg Tablets: None or associated with Lennox-
Inovelon® in EU and Japan (2) (2) b.i.d. Colloidal silicon dioxide tablets can be Gastaut Syndrome (LGS)
Oral Suspension/ Oral suspension: 40 mg/ dose volume: 0.125- Corn starch swallowed whole,
Room temperature/ mL 0.56 mL/kg up to 40 Croscarmellose sodium cut in half or crushed
Bottle mL Hypromellose (2)
Lactose monohydrate Oral suspension:
Magnesium stearate none
Microcrystalline cellulose
preservative-free

R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365

(2) Oral suspension: Micro-
crystalline cellulose

Carboxymethylcellulose
sodium
Hydroxyethyl cellulose
Citric acid
Simethicone emulsion
Poloxamer 188
Methylparaben
Propylparaben
Propylene glycol
Potassium sorbate
Sorbitol solution 70% (~30%
water)
Orange flavor
200 mg tablet, scored

Tenofovir disoproxil fumarate/Viread®/ Tablets/Room 150 mg, 200 mg, 250 mg, 17-22 g: 150 mg Croscarmellose sodium None Gilead Sciences/Antiviral
2017 (150 mg, 200 mg, 250 mg temperature/Bottle 300 mg 22-28 kg: 200 mg Lactose monohydrate
tablets)/EU, USA, Japan 28-35 kg: 250 mg Magnesium stearate
35 kg: 300 mg Microcrystalline cellulose
qd Pregelatinized starch
preservative-free
(continued on next page)

1347
 1348 R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365

100 mg, or 150 mg using unit dose tablets of 25 mg and a scored

Medicure Pharma, Inc./ACE

inhibitor - hypertension
100 mg of a preservative-free formulation of ammonium hydrox-
ide, crospovidone, ethylcellulose 20 cP, fructose, hydroxypropyl
Company/Indication

cellulose, hypromellose 2910/6cP, magnesium stearate, mannitol,

medium chain triglycerides, monoammonium glycyrrhizinate,
natural flavors (orange, banana, with aspartame), oleic acid, PEG
400, saccharin sodium, sodium citrate, sodium stearyl fumarate,
sorbitol, sucralose, and yellow iron oxide. See Isentress® powder for
oral suspension for a measurable dosage form.

Mini-Tablets
Desitin® (levetiracetam) mini-tablets from Desitin Pharmaceu-
ticals GmbH was approved in 2011 for the treatment of seizures in
epilepsy for children aged >6 years with a twice-daily dose 10-30
Preparation

mg/kg using unit dose stick packs of 250 mg, 500 mg, or 1000 mg
None

per packet of a preservative-free formulation containing povidone

K30, microcrystalline cellulose, silica colloidal anhydrous, magne-
sium stearate, poly(vinyl alcohol), titanium dioxide, PEG 3350, and
talc. The entire packet of Desitin® (levetiracetam) mini-tablets is
administered orally. The Desitin® mini-tablets are 2 mm in diam-
Listed in Package Insert)
Inactive in Formulation (as

eter with 5 mg levetiracetam per mini-tablet.

Potassium sorbate
Propylene glycol

Oral Formulations Requiring Maninuplation

Methylparaben
Poloxamer 188

Sodium citrate
Grape flavor

Sucralose

Pediatric oral formulations that require manipulation are

Water

available as many types including concentrated suspension, pow-

der for oral solution, powder for oral suspension, granules for oral
suspension, multiple types of tablets including scored tablet,
dose volume: 0.16-0.34
0.65-1.35 mg/kg (up to

dispersible scored tablet, tablet for oral suspension, and multiple

mL/kg (up to 10-40
40-160 mg) (b)i.d.

microparticulates including sprinkle capsules, oral powder, oral

granules, and manipulated mini-tablets. Table 4 is a listing of
identified pediatric oral formulations that require manipulation
and were commercialized between the years 2007 and mid-2018.
mL)
Dose

Multiparticulates

Multiparticulates include sprinkle capsules, oral powders, oral

granules, and a manipulated mini-tablet.
Active in Formulation

Sprinkle Capsules
Powder filled into 2-piece gelatin or hydroxypropyl methylcel-
lulose capsules can be sprinkled onto soft foods or added to drinks.
4 mg/mL

Sustiva® (efazirenz) from Bristol-Meyers Squibb is an antiviral

and is available in 50 mg and 100 mg 2-piece hard gelatin capsules
that can be opened and the contents added to 1-2 teaspoons of
Marketed Formulation/

120 mL and 473 mL

soft food such as applesauce, grape jelly, yogurt, or 10 mL of infant

temperature/Bottle,
Oral Solution/Room

formula in a small container and then administered with a spoon

Storage/Package

or syringe. The preservative-free composition includes lactose

monohydrate, magnesium stearate, sodium lauryl sulfate, and
sodium starch glycolate.
Cholbam® (cholic acid) from Manchester Pharmaceutical was
approved in 2015 for the treatment of bile acid synthesis disorders
due to single enzyme defects with a once-daily dose or divided into
Diovan in Europe, 3 mg/mL (160 mL)

2 dose of 10-15 mg/kg using a unit dose 2-piece capsule of 50 mg of

a preservative-free formulation containing silicified microcrystal-
Valsartan/Prexxartan™/2017/USA
Drug Name/Marketed Name/Year

line cellulose, magnesium stearate. To mask any unpleasant taste,

the Cholbam® capsule(s) can be opened and the contents mixed
with 15-30 mL of either infant formula or expressed breast milk (for
approved/Country

younger children) or soft food such as mashed potatoes or apple

Table 3 (continued )

puree (for older children and adults).

Nexium® (esomeprazole magnesium) from AstraZeneca was
by Novartis

approved in 2007 for the treatment of gastroesophageal reflux

disease (GERD) with a once-daily dose of 10-40 mg using unit
dose 2-piece delayed-release capsules of 20 mg or 50 mg of a
preservative-free formulation that is enteric-coated granules
Table 4
Pediatric Formulations Marketed since 2007: Manipulation Required
Drug Name/Marketed Marketed Formulation/Storage/
Name/Year Package
approved/Country
Atazanavir sulfate/ Oral powder/Packet: Room
Reyataz®/2014/EU, temperature
USA Mixed with food: 1 h at room
temperature/Packet
Artemether and Dispersible tablets/Tablets:
Lumefantrine/ Room temperature
Coartem®/2009/USA Constituted suspension:
Riamet® in EU consume immediately/
Blisters
Azithromycin/Zmax®/ Single-use Prolonger-release
2013/USA granules for oral suspension/
Sumamed® in EU Bottle/Before constitution:
room temperature.
After constitution: room
temperature for maximum
12 d, after which the
remaining suspension is to
be discarded.
Bosentan/Tracleer®/ Tablets for oral suspension/
2017/EU, USA, Japan Room temperature
Divided tablet pieces: 20 C-
25 C in the opened blister for
up to 7 d.
Constituted suspension
(dispersed tablet): consume
immediately/Blister
Active in Formulation Dose
50 mg per packet (1.5 grams 200-250 mg (4 or 5 packets)
powder, thus 3.33% w/w Must be taken with
atazanavir sulfate) ritonavir
20 mg/120 mg scored tablet 1-3 tablets (b)i.d. for 3 d
Constituted suspension: 27 mg/mL 60 mg/kg up to 2.0 grams
Dose volume: 2.2 mL/kg (1
mL per pound body
weight)
32 mg, quadrisected 16 mg-64 mg (b)i.d.
Inactive in Formulation (as Preparation Company/Indication
Listed in Package Insert)
Aspartame Mixed with food such Bristol-Meyers Squibb/
Sucrose as applesauce or Antiviral
Orange-vanilla flavor yogurt or infant
preservative-free formula
Colloidal silicon dioxide None or tablets may be Novartis/treatment of
Croscarmellose sodium crushed and mixed acute,
Hypromellose with 1 to 2 teaspoons uncomplicated
Magnesium stearate of water in a clean malaria infections
Microcrystalline cellulose container due to Plasmodium
Polysorbate 80 falciparum
preservative-free
R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365
Lipid nanoparticle: Constitute with 60 mL Pfizer/Antibacterial
Glyceryl behenate water
Poloxamer 407
Sucrose
Sodium phosphate
Magnesium hydroxide
Hydroxypropyl cellulose
Xanthan gum
Colloidal silicon dioxide
Titanium dioxide
Artificial cherry flavor
Artificial banana flavor
preservative-free
Microcrystalline cellulose Disperse intact tablet or Actelion
Calcium hydrogen scored tablet in a Pharmaceuticals US,
phosphate minimal amount of Inc./Treatment of
Croscarmellose sodium water immediately pulmonary arterial
Silica colloidal before hypertension
Tartaric acid administration
Tutti-frutti flavor
Aspartame
Acesulfame potassium
(continued on next page)
1349
Table 4 (continued )
Drug Name/Marketed Marketed Formulation/Storage/
Name/Year Package
approved/Country
Carglumic acid/ Tablet for oral suspension/
Carbaglu®/2010/EU, Tablets: Refrigerated 2 C-
USA 8 C, after opening 1 mo at
room temperature
Constituted suspension:
consume immediately/Bottle
Cholic acid/Cholbam®/ Sprinkle capsule/Capsule:
2015/EU, USA Room temperature
Mixed with food: consume
immediately/Bottle
Clobazam/Onfi®/2011/ Tablet/Room temperature/
USA Bottle
Active in Formulation Dose Inactive in Formulation (as
Listed in Package Insert)
Magnesium stearate
preservative-free
200 mg, triple scored tablet 100-250 mg/kg/d divided Croscarmellose sodium
into 2 or 4 doses Hypromellose
Microcrystalline cellulose
Silica colloidal anhydrous
Sodium lauryl sulfate
Sodium stearyl fumarate
preservative-free
50 mg 10-15 mg/kg qd or divided Silicified microcrystalline
into 2 dosed cellulose
Magnesium stearate
preservative-free
5 mg (discontinued), 10 mg scored, 5 mg-40 mg Corn starch
20 mg scored Lactose monohydrate
Magnesium stearate
1350
Preparation Company/Indication
Constitute in a small Recordati Rare Diseases
cup with 2.5 mL Inc./Chronic
R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365
water per tablet, stir, hyperammonemia
administer either as due to deficiency of
a drink, through a the hepatic enzyme
syringe or N-acetylglutamate
nasogastric tube. synthase (NAGS).
Capsules can be opened Asklepion
and the contents Pharmaceuticals LLC
mixed with 15-30 or Manchester
mL of either infant Pharmaceuticals, Inc.
formula or expressed a wholly owned
breast milk (for subsidiary of
younger children), or Retrophin, Inc./
soft food such as Treatment of bile
mashed potatoes or acid synthesis
apple puree (for disorders due to
older children and single-enzyme
adults) to mask any defects
unpleasant taste
None, scored, or Lundbeck/Anti-seizure
crushed and mixed only with Lennox-
with applesauce
 Frisium® in EU by Silicon dioxide Gastaut syndrome
Aventis Talc (LGS)
preservative-free
Frisium® 10 mg Onfi® tablet

Deflazacort (prodrug of 1 Tablet, 2 Oral suspension/1 (1) 0.9 mg/kg (1) Tablet (1) Marathon
corticosteroid, 21- Room temperature, 2 Room Tablets: 6 mg, 18 mg, 30 mg, 36 (1) Tablets: None or Pharmaceuticals, LLC
desDFZ)/Emflaza™/ temperature, discard after 1 mg Tablet: round up to the Colloidal silicon dioxide crushed and taken (and later acquired
2018/USA mo of first opening/1 Bottle, (2) nearest possible dose immediately after by PTC

R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365

Lactose monohydrate
Calcort® in EU by 2 Bottle: 13 mL in 20 mL Oral suspension: 22.75 mg/mL (2) Magnesium stearate mixing with Therapeutics)/
Sanofi Aventis bottle, with 2 1 mL oral Oral suspension: round Pregelatinized corn starch applesauce. Duchenne muscular
dispensers up to the nearest tenth of preservative-free (2) dystrophy (DMD)
a mL Oral suspension:
(2) Oral suspension
dose volume: 0.04 mL/kg Slowly add to 3 to 4
ounces of juice or
Acetic acid
milk and mix well,
Aluminum magnesium
administer
silicate
immediately, do not
Benzyl alcohol
administer with
Carboxymethylcellulose
grapefruit juice.
sodium
Polysorbate 80
Sorbitol
Water

Efavirenz/Sustiva® Sprinkle capsule/Capsule:
capsule for oral use/ Room temperature
2013/EU, USA Mixed with food: 30 min room
temperature/Bottle
50 mg and 200 mg 100 mg-600 mg Contents of capsule: Open capsule(s) and
Lactose monohydrate
Magnesium stearate
Sodium lauryl sulfate
Sodium starch glycolate
preservative-free
Bristol-Meyers Squibb/
add contents to 1-2 Antiviral
teaspoons of soft
food such as
applesauce, grape
jelly, yogurt, or 10
mL of infant formula
in a small container.
Administer with a
spoon or syringe.
(continued on next page)

1351
Table 4 (continued )

1352
Drug Name/Marketed Marketed Formulation/Storage/ Active in Formulation Dose Inactive in Formulation (as Preparation Company/Indication
Name/Year Package Listed in Package Insert)
approved/Country

Enalapril/Epaned™/ Powder for Oral Solution/Room 150 mg per bottle, reconstituted to 0.08 mg/kg up to 5 mg QD Mannitol Reconstitute with 150 Silvergate
2013/USA temperature/Kit: 1 mg/mL dose volume: 0.08 mL/kg Colloidal silicon dioxide mL of the provided Pharmaceuticals,
1 bottle of powder preservative-free diluent Inc./Hypertension
1 bottle of Ora-Sweet SF diluent
Eltrombopag/ Powder for oral suspension/ 25 mg per packet 25 mg or 50 mg, adjust dose Mannitol Constitute with 20 mL GlaxoSmithKline/
Promacta®/2015/ Before constitution: room to maintain platelet Sucralose cold water, and Thrombocytopenia
USA temperature. count greater than or Xanthan gum consume
Revolade® in EU and After constitution: 30 min/Kit: equal to 50  109/L. preservative-free immediately
Japan 30 packets, 1 reusable bottle
with lid and cap (pictured),
and 1 reusable 20-mL oral
syringe

R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365

Esomeprazole (1) (1) 10 mg-40 mg qd (1) Capsules, active (1) Capsules: AstraZeneca/
magnesium/ Delayed-release capsules/ 20 mg, 40 mg enteric-coated Gastroesophageal
Nexium®/2007/EU, Room temperature/Bottles (2) granules, (white to pale Nasogastric tube: Add reflux disease
USA, Japan (2) 10 mg, 20 mg, 40 mg per packet brown color) contents of capsule (GERD)
For delayed-release oral sus- Esomeprazole is unstable in acidic to 50 mL water in a
pension/For oral suspension: media Glyceryl monostearate 60-mL catheter-
Room temperature Hydroxypropyl cellulose tipped syringe, shake
Constituted suspension: Hypromellose well for 15 s, attach
30 min/Packets Magnesium Stearate to nasogastric tube,
Methacrylic acid copolymer administer.
Polysorbate 80 Food: Add contents of a
Sugar spheres capsule to
Talc applesauce,
Triethyl citrate administer
preservative-free (2) For oral
(2) For oral suspension: suspension:
active enteric-coated
granules same as in Nasogastric tube: Add
capsule, and inactive 15 mL water to a
granules (pale yellow catheter-tipped sy-
color): ringe, add contents
of a packet, shake, let
Dextrose the suspension stand
Xanthan gum for 2-3 min to

Everolimus/Afinitor® Tablet for Oral Suspension/
Disperz™/2012/USA Blisters: Room temperature
Votubia® in Europe Constituted suspension:
administer immediately after
preparation/Blisters
Hydroxyurea/Siklos®/ Tablet/Tablets: Room
2018/EU, USA temperature
Broken 1000 mg tablets must
be stored in the bottle and
must be used within 3 mo/
Bottles
2 mg, 3 mg, 5 mg
100 mg, 1000 mg triple scored
(pictured)
Crospovidone thicken, attach to
Citric acid nasogastric tube,
Iron oxide administer
Hydroxypropyl cellulose Water: Empty contents
preservative-free of a packet into a
container with 15 mL
water, stir, let the
suspension stand for
2-3 min to thicken,
drink within 30 min
R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365
5 mg/kg2, or adjust dose to Butylated hydroxytoluene Add tablets to the Novartis
attain trough Colloidal silicon dioxide syringe, pull in Pharmaceuticals
concentrations of 5-15 Crospovidone water, mix to Corp/TSC-associated
ng/mL Hypromellose constitute to a partial-onset
Adjust dose by number of Lactose monohydrate suspension, let stand seizures
tablets Magnesium stearate for 3 min, then
Mannitol administer
Microcrystalline cellulose Gently invert the
preservative-free syringe 5 times
immediately prior to
administration
Tablet must be
dispersed in water…
not swallowed
whole, chewed or
crushed
15-30 mg/kg qd Silicified microcrystalline None, score the 1000 Addmedica/
cellulose mg tablet, or Antimetabolite,
Sodium stearyl fumarate dispersed indicated to reduce
Film-coating agent amino immediately before the frequency of
methacrylate copolymer use in a small painful crises and to
preservative-free quantity of water in a reduce the need for
1353
(continued on next page)
Table 4 (continued )
Drug Name/Marketed Marketed Formulation/Storage/
Name/Year Package
approved/Country
1000 mg triple-scored tablet
Ivacaftor/KALYDECO®/ Oral granules (mini-tablets)/
2015/EU, USA granules: room temperature
Mixed with food: 1 h (therefore
should be consumed during
this 1-h period)/Unit-dose
packets/Packets
Losartan potassium/ Tablet/Tablet: room
Cozaar®/2012/EU, temperature
USA Constituted suspension: 2 C-
Nu-Lotan in Japan by 8 C for 4 wk/Bottle
Active in Formulation Dose
50 mg or 75 mg per packet One 50 mg or 75 mg packet
(b)i.d.
Just before and just after
fat-containing food
25 mg, 50 mg (scored, pictured) or 0.7 mg/kg up to 50 mg total
100 mg dose volume: 0.28 mL/kg
Inactive in Formulation (as
Listed in Package Insert)
Colloidal silicon dioxide
Croscarmellose sodium
Hypromellose acetate
succinate
Lactose monohydrate
Magnesium stearate
Mannitol
Sucralose
Sodium lauryl sulfate
preservative-free
Sweetened but unflavored
Microcrystalline cellulose
Lactose
Pregelatinized starch
Magnesium stearate
Hydroxypropyl cellulose
1354
Preparation Company/Indication
teaspoon. Adding a blood transfusions in
drop of syrup or pediatric patients, 2
mixing with food can y of age and older,
mask a possible with sickle cell
bitter taste. anemia with
recurrent moderate-
to-severe painful
crises
R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365
Each packet mix with 1 Vertex/cystic fibrosis
teaspoon (5 mL) of
age-appropriate soft
food or liquid at or
below room
temperature, then
follow with fatty
food.
2.5 mg/mL suspension: Merck/Anti-
Add 10 mL water to a hypertension
240-mL PET bottle,
add ten 50 mg
tablets, shake for
 Banyu
Pharmaceuticals
Lumacaftor and Oral granules/RT/Packets, every
Ivacaftor/Orkambi®/ carton has 56 Orkambi® oral
2015/USA granule packets, organized in
4 weekly wallets. Each wallet
has 2 packets for each of the
7 d in a wk.
Nilotinib HCl/Tasigna®/ Sprinkle capsule/Capsule: room
2018/USA temperature
Mixed with food: 15 min,
consume immediately/Bottle
Lumacaftor 100 mg and ivacaftor
125 mg or Lumacaftor 150 mg
and ivacaftor 188 mg
50 mg
Hypromellose 2 min, let stand 1 h,
Titanium dioxide shake 1 min, add 190
preservative-free of a 50/50 mixture of
Ora-Plus and Ora-
Sweet, shake for
1 min
R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365
Age 2 through 5 y and Microcrystalline cellulose Mixed contents of a Vertex/Treatment of
weighing less than 14 kg: Croscarmellose sodium packet with 1 cystic fibrosis in
1 packet of granules Hypromellose acetate teaspoon (5 mL) of patients age 2 y and
(each containing succinate soft food or liquid older who have 2
lumacaftor 100 mg/ Povidone and administered copies of the F508del
ivacaftor 125 mg, (b)i.d. Sodium lauryl sulfate orally every 12 h mutation (F508del/
Age 2 through 5 y and preservative-free with fat-containing F508del) in their
weighing 14 kg or food. CFTR gene
greater: 1 packet of Consume within 1 h of
granules (each preparation
containing lumacaftor
150 mg/ivacaftor 188
mg), (b)i.d.
After administering
Orkambi® consume fat-
containing food.
230 mg/m2 rounded to the Colloidal silicon dioxide Contents of each Novartis/Treatment of
nearest 50 mg dose (to a Crospovidone capsule dispersed in Philadelphia
maximum single dose of Lactose monohydrate 1 teaspoon of chromosome
400 mg) b.i.d. Magnesium stearate applesauce. epositive chronic
(continued on next page)
1355
Table 4 (continued )

1356
Drug Name/Marketed Marketed Formulation/Storage/ Active in Formulation Dose Inactive in Formulation (as Preparation Company/Indication
Name/Year Package Listed in Package Insert)
approved/Country

Poloxamer 188 myeloid leukemia

preservative-free (Ph þ CML)
Oseltamivir phosphate/ Sprinkle capsule/Room 30 mg, 45 mg, 75 mg 3 mg/kg up to 75 mg (b)i.d. Croscarmellose sodium TAMIFLU capsules may Gilead Sciences and
Tamiflu®/2007/EU, temperature/Blisters for 5 d Povidone K30 be opened and Genentech/Antiviral
USA, Japan Pregelatinized starch mixed with
Sodium stearyl fumarate sweetened liquids
Talc such as regular or
preservative-free sugar-free chocolate
syrup, corn syrup,
caramel topping, or
light brown sugar
(dissolved in water).
Pantoprazole sodium/ Granules for delayed-release 40 mg per packet 15-40 kg: 20 mg Enteric-coated granules: Because proper pH is Wyeth (now Pfizer)/
Protonix®/2007/USA oral suspension/Room >40 kg: 40 mg Crospovidone necessary for Treatment of erosive

R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365

temperature/Packet
Rabeprazole sodium/ Sprinkle capsule/Capsule: room
AcipHex® Sprinkle™ temperature
Hypromellose
Methacrylic acid copolymer
Microcrystalline cellulose
Polysorbate 80
Povidone
Sodium carbonate
Sodium lauryl sulfate
Talc
Titanium dioxide
Triethyl citrate
Yellow ferric oxide
preservative-free
5 mg or 10 mg 10-20 mg qd In a hydroxypropyl
Enteric-coated granules, methylcellulose capsule:
stability, do not esophagitis
administer associated with
PROTONIX. For Gastroesophageal
delayed-release, oral Reflux Disease
suspension in liquids (GERD)
other than apple
juice, or foods other
than applesauce.
Applesauce: Sprinkle
granules on 1
teaspoonful of
applesauce.
Apple juice: Empty
granules into a small
cup or teaspoon
containing 1
teaspoon of apple
juice. Stir for 5 s
(granules will not
dissolve) and
swallow
immediately.
Nasogastric tube:
Empty the contents
of the packet into the
barrel of the syringe,
Add 10 mL (2
teaspoonfuls) of
apple juice and
gently tap and shake
the barrel of the
syringe to help rinse
the syringe and tube.
Repeat at least twice
more using the same
amount of apple
juice (10 mL or 2
teaspoonfuls) each
time.
Open capsule(s) and Eisai/Treatment of
add contents to a gastroesophageal
 delayed-release Mixed with food: 15 min room
capsules/2013/USA temperature/Bottle
Raltegravir/Isentress®/ Powder for oral suspension/
2014/EU, USA Packets: Room temperature
Constituted suspension: 30 min
at room temperature/Kit:
Each carton has: 60 packets, 2
reusable mixing cups with
lids, 2 reusable 5-mL dosing
syringes
Tacrolimus/Prograf® Granules for Oral Suspension/
Granules/2009/USA, Packets: Room temperature
Japan Constituted oral suspension:
Modigraf in EU consume immediately/
Packets
rabeprazole is unstable in acidic Colloidal silicon dioxide
media Diacetylated
monoglycerides
Ethylcellulose
Hypromellose
Hypromellose phthalate
Magnesium stearate
Mannitol
Talc
Titanium dioxide
preservative-free
100 mg per packet, constituted to 6 mg/kg/dose Ammonium hydroxide Constitute 1 packet
20 mg/mL suspension dose volume: 0.30 mL/kg Banana with other natural
flavors
Carboxymethylcellulose
sodium
Crospovidone
Ethylcellulose 20 cP
Fructose
Hydroxypropyl cellulose
Hypromellose 2910/6cP
PEG 400
Magnesium stearate
Maltodextrin
Mannitol
Medium chain triglycerides
Microcrystalline cellulose
Monoammonium
glycyrrhizinate
Oleic acid
Sorbitol
Sucralose
Sucrose
preservative-free
0.2 mg, 1 mg 0.075-0.15 mg/kg (b)i.d. Croscarmellose sodium Add contents of packet
Hypromellose
Lactose monohydrate
preservative-free
small amount of soft reflux disease
food such as (GERD)
applesauce, baby
food or yogurt, or a
small amount of
infant formula, apple
juice in a small
container.
Administer with a
spoon or syringe.
Merck/Antiviral
with 5 mL water to
20 mg/mL
suspension in the
supplied mixing cup,
measure dose and
administer
R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365
Astellas Pharma Inc./
to 15-30 mL water, immunosuppressant
stir, administer the indicated for the
suspension prophylaxis of organ
immediately, or the rejection in patients
suspension can be receiving allogeneic
drawn up via a non- liver, kidney, or heart
PVC oral syringe. transplants
(continued on next page)
1357
Table 4 (continued )

1358
Drug Name/Marketed Marketed Formulation/Storage/ Active in Formulation Dose Inactive in Formulation (as Preparation Company/Indication
Name/Year Package Listed in Package Insert)
approved/Country

R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365

Tenofovir disoproxil Oral powder/Powder: Room
fumarate/Viread® temperature
Oral Powder/2011/ Mixed with food: consume
EU, USA immediately/Bottle, with
custom-made scoop
40 mg per 1 gram powder, 1 level Oral powder: 8 mg/kg up to Ethylcellulose,
scoop is 1.0 grams of powder 300 mg (2-7.5 scoops) qd Hydroxypropyl cellulose
Mannitol,
Silicon dioxide
preservative-free
Use the provided Gilead Sciences/
custom-made scoop Antiviral
and add the powder
to 1/4-1/2 cup of soft
foods

Terbinafine HCL/ Oral granules (mini-tablets)/
Lamisil®/2007/USA Room temperature/Stick
packets
125 mg or 187.5 mg per stick packet
125 mg/d for <25 kg body Basic butylated
mass; 187.5 mg/d for 25- methacrylate copolymer
35 kg Colloidal silicon dioxide
Dibutyl sebacate
Hypromellose USP
Magnesium stearate
Microcrystalline cellulose
Nitrogen (filling gas)
Polyethylene glycol
Sodium lauryl sulfate
Sodium starch glycolate
preservative-free
Pour entire contents of Novartis/Treatment of
stick packet onto a tinea capitis, fungal
spoonful of a soft infection of scalp
food, such as
pudding or other
soft, nonacidic food
such as mashed
potatoes. Do not use
applesauce or a fruit-
based food.
Make sure that no
granules remain in
the stick packet.
Swallow combination
of food and granules
without chewing
Uridine triacetate Oral granules/Room 95% uridine triacetate Xuriden™: Only 5% inactive Need a scale to measure Wellstat Therapeutics
(prodrug of uridine, temperature/Packets, 30 per Xuriden™: 2 grams per packet, 60-120 mg/kg (not to ingredients at 0.1 gram accuracy, Corporation/
Vistogard®: 10 grams per packet.

R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365

which has 4- to 6- carton exceed 8 grams), 103 mg per Xuriden™ or a graduated Hereditary orotic
fold higher oral 0.4-6 grams, packet teaspoon. aciduria (Xuriden™)
bioavailability than 1/8-2 teaspoons qd Ethylcellulose, 62 mg Weigh the prescribed or following a
uridine/Xuriden™ Vistogard®: Opadry, 15 mg dose to at least 0.1 fluorouracil or
and Vistogard®/ 6.2 grams/m2/dose, natural orange juice flavor, gram, or a graduated capecitabine
2015/USA 2.1-10 grams, 1-4 26 mg teaspoon accurate to overdose
teaspoons q.i.d 517 mg per Vistogard® the fraction of the (Vistogard®)
packet dose.
Ethylcellulose, 309 mg Administer dose with
Opadry, 77 mg soft food
Natural orange juice flavor, (applesauce,
131 mg pudding, or yogurt)
preservative-free or in milk or infant
formula within
30 min

Vancomycin HCl/ Powder for oral solution/Before
Firvanq™/2018/USA reconstitution at refrigerated
conditions, 2 C to 8 C (36 F
to 46 F). Do not freeze.
Reconstitute solution at 2 C
to 8 C and discard after 14
d or if it appears hazy or
contains particulates/Kit:
Bottle of powder for oral
solution (150 mL or 300 mL),
25 mg/mL or 50 mg/mL on 40 mg/kg t.i.d or q.i.d. for 7 Artificial grape flavor Transfer about half the CutisPharma/
reconstitution; to 10 d. The total daily Citric acid contents of the Antibacterial:
3.75 g, 7.5 g or 15 g per bottle, dosage should not D&C yellow no. 10 grape-flavored Clostridium difficile
exceed 2 g. FD&C red no. 40 diluent into the eassociated diarrhea
Dose volume Sodium benzoate vancomycin and enterocolitis
50 mg/mL: 0.8 mL/kg t.i.d or Sucralose hydrochloride USP caused by
q.i.d. Water powder bottle, shake Staphylococcus
25 mg/mL: 1.6 mL/kg, t.i.d bottle vertically for aureus, including
or q.i.d. approximately 45 s, methicillin-resistant
add the remaining strains

1359
(continued on next page)
Table 4 (continued )

1360
Drug Name/Marketed Marketed Formulation/Storage/ Active in Formulation Dose Inactive in Formulation (as Preparation Company/Indication
Name/Year Package Listed in Package Insert)
approved/Country

and a bottle of premeasured grape-flavored

Grape-flavored diluent diluent, shake the
bottle for
approximately 30 s.
Vigabatrin/Sabril®/ Powder for oral solution/Room 500 mg per packet, constituted to Initial daily dose is 50 mg/ Povidone (simple Constitute a packet Lundbeck/infantile
2016/EU, USA temperature/Packets 50 mg/mL kg/d given in 2 divided formulation) with 10 mL water spasms
Generic: Vigabatrin doses (25 mg/kg twice preservative-free Generic: Par
for oral solution, daily); subsequent Pharmaceutical
USP, 500 mg, in 2017 dosing can be titrated by
25 mg/kg/d to 50 mg/kg/
d increments every 3 d,
up to a maximum of 150
mg/kg/d given in 2
divided doses (75 mg/kg

R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365

twice daily)
dose volume per dose:
0.25-1.5 mL/kg

Generic: Vigabatrin for oral solution, USP, 500 mg

 R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365
containing glyceryl monostearate, hydroxypropyl cellulose,
hypromellose, magnesium stearate, methacrylic acid copolymer,
polysorbate 80, sugar spheres, talc, and triethyl citrate. The
capsule contents can be used to prepare a suspension that can be
administered by a nasogastric tube. The contents of a Nexium®
delayed-release capsule can be added to 50 mL of water in a 60-
mL catheter tipped syringe, then shaken well for 15 s, attached
to a nasogastric tube, and then administered. Alternatively, the
contents of a Nexium® delayed-release capsule can be added to
applesauce and then administered.
Tasigna® (nilotinib HCl) from Novartis was approved in 2018 for
the treatment of Philadelphia chromosomeepositive chronic
myeloid leukemia (Ph þ CML) with a twice-daily dose of 230 mg/
m2 rounded to the nearest 50 mg dose (to a maximum single dose
of 400 mg) using a unit dose 50 mg 2-piece capsule of a
preservative-free formulation containing colloidal silicon dioxide,
crospovidone, lactose monohydrate, magnesium stearate, and
poloxamer 188. Contents of each Tasigna® capsule can be dispersed
in 1 teaspoon of applesauce, and then administered.
Tamiflu® (oseltamivir phosphate) from Roche is an antiviral
with a twice daily dose of 3 mg/kg up to 75 mg for 5 days using unit
dose 2-piece capsules of 30 mg, 45 mg, or 75 mg of a preservative-
free formulation containing croscarmellose sodium, povidone K30,
pregelatinized starch, sodium stearyl fumarate, and talc. The
Tamiflu® capsules may be opened and mixed with sweetened liq-
uids such as regular or sugar-free chocolate syrup, corn syrup,
caramel topping, or light brown sugar (dissolved in water).
AcipHex® Sprinkle™ delayed-release capsules (rabeprazole so-
dium) from Eisai was approved in 2013 for the treatment of GERD
with a once-daily dose of 10-20 mg using unit dose hydroxypropyl
methylcellulose capsules of 5 mg or 10 mg of enteric-coated
granules with a preservative-free formulation containing colloidal
silicon dioxide, diacetylated monoglycerides, ethylcellulose,
hypromellose, hypromellose phthalate, magnesium stearate,
mannitol, talc, and titanium dioxide. The AcipHex® Sprinkle™
capsule(s) are opened and the contents added to a small amount of
soft food such as applesauce, baby food or yogurt, or a small
amount of infant formula, apple juice in a small container, and then
administered with a spoon or syringe.
Oral Powder
Reyataz® (atazanavir sulfate) oral powder, packaged in unit-
dose sachets, from Bristol-Meyers Squibb is an antiviral was
approved in 2014 with a dose of 200-250 mg using 4 or 5 packets of
50 mg per packet of a preservative-free formulation containing
aspartame, sucrose, and orange-vanilla flavor. The Reyataz® (ata-
zanavir sulfate) packets are opened, and the contents mixed with
food such as applesauce or yogurt or infant formula. Each 50 mg
packet is filled with 1.5 grams of powder, making the formulation
3.33% w/w atazanavir sulfate.
Viread® (tenofovir disoproxil fumarate) oral powder, packaged
in a bottle, from Gilead Sciences was approved in 2011 as an anti-
viral with a once-daily dose of 8 mg/kg up to 300 mg (2-7.5 scoops)
of a preservative-free taste-masked formulation containing
mannitol, hydroxypropyl cellulose, ethylcellulose, and silicon di-
oxide. The provided custom-made scoop is used to measure the
dose that is then added to 1/4 to 1/2 cup of soft foods.
Oral Granules
Xuriden™ and Vistogard® (uridine triacetate, a prodrug of uri-
dine that has 4- to 6-fold higher oral bioavailability than uridine)
oral granules from Wellstat Therapeutics Corporation was
approved in 2015 for the treatment of hereditary orotic aciduria
(Xuriden™) or following a fluorouracil or capecitabine overdose
(Vistogard®). The dose and dose frequency are different for each
1361
product and indication. The once-daily dose of Xuriden™ is 60-120
mg/kg not to exceed 8 grams (0.4-6 grams, 1/8-2 teaspoons). The 4
timesedaily dose of Vistogard® is 6.2 grams/m2/dose (2.1-10 grams,
1-4 teaspoons). To prepare the doses of Xuriden™ and Vistogard®, a
scale is needed that measures at 0.1-gram accuracy or a graduated
teaspoon. Weigh the prescribed dose to at least 0.1 gram or a
graduated teaspoon accurate to the fraction of the dose. Administer
dose with soft food (applesauce, pudding, or yogurt) or in milk or
infant formula within 30 min. The oral granule preservative-free
formulation is 95% uridine triacetate and approximately 3% ethyl-
cellulose, 0.8% Opadry coating, and 1.2% natural orange juice flavor.
Orkambi® oral granules is a fixed-dose combination of luma-
caftor and ivacaftor (100 mg and 125 mg, or 150 mg and 188 mg)
from Vertex and approved in 2015 for the treatment of cystic
fibrosis with a twice-daily dose determined by age and body mass
with age 2-5 years and <14 kg a dose of 1 packet of 100 mg
lumacaftor and 125 mg ivacaftor; and with age 2-5 years and 14
kg, a dose of 1 packet of 150 mg lumacaftor and 188 mg ivacaftor. To
prepare the dose, add the contents of 1 packet to 1 teaspoon (5 mL)
of soft food or liquid (Fig. 8) and administered orally every 12 h with
fat-containing food. Consume the mixture within 1 h of prepara-
tion. The Orkambi® oral granules have the same composition of the
tablets except without magnesium stearate and is a preservative-
free formulation containing microcrystalline cellulose, cro-
scarmellose sodium, hypromellose acetate succinate, povidone, and
sodium lauryl sulfate. See Orkambi® tablets for ages 6 years.
Mini-Tablets (Oral Granules)
Lamisil® (terbinafine HCl) oral granules are mini-tablets that are
packaged into sachets with nitrogen filling gas. Lamisil® oral gran-
ules were approved in 2007 and are from Novartis for the treatment
of tinea capitis, fungal infection of the scalp. The daily terbinafine HCl
dose is 125 mg for <25 kg body mass or 187.5 mg for 25-35 kg body
mass using a 125 mg or 187.5 mg stick packet that have multiple
mini-tablets in a preservative-free formulation containing basic
butylated methacrylate copolymer, colloidal silicon dioxide, dibutyl
sebacate, hypromellose USP, magnesium stearate, microcrystalline
cellulose, nitrogen (filling gas), polyethylene glycol, sodium lauryl
Figure 8. Orkambi® (lumacaftor/ivacaftor) oral granules.38
1362 R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365
sulfate, and sodium starch glycolate. To use Lamisil® oral granules,
pour the entire contents of a stick packet onto a spoonful of a soft
food, such as pudding or other soft, nonacidic food such as mashed
potatoes. Do not use applesauce or a fruit-based food. Make sure that
no granules remain in the stick packet. Swallow combination of food
and granules without chewing.
Kalydeco® (ivacaftor) oral granules, which appears to be mini-
tablets and packaged in sachets, is from Vertex and was approved
in 2015 for the treatment of cystic fibrosis with a twice-daily dose of
one 50 mg or 75 mg packet just before and just after fat-containing
food. Kalydeco® oral granules is a preservative-free formulation
containing colloidal silicon dioxide, croscarmellose sodium, hypro-
mellose acetate succinate, lactose monohydrate, magnesium stea-
rate, mannitol, sucralose, and sodium lauryl sulfate. Each packet of
Kalydeco® oral granules is mixed with 1 teaspoon (5 mL) of age-
appropriate soft food or liquid at or below room temperature and
then administered within 1 h. A video is available showing the drug
product and manipulation with soft foods.39
Oral Suspension, Concentrate to Be Diluted
Emflaza™ (deflazacort, prodrug of corticosteroid, 21-desDFZ)
oral suspension originally developed by Marathon Pharmaceuti-
cals, LLC was approved in 2018 for the treatment of Duchenne
muscular dystrophy with a dose of 0.9 mg/kg rounded up to the
nearest tenth of a mL using a dose volume of 0.04 mL/kg of a
concentrated 22.75 mg/mL oral suspension with a formulation
containing acetic acid, aluminum magnesium silicate, benzyl
alcohol, carboxymethyl-cellulose sodium, polysorbate 80, sorbitol,
and water. The Emflaza™ concentrated oral suspension is slowly
added to 3-4 ounces of juice or milk and mixed well and admin-
istered immediately; do not administer with grapefruit juice.
Powder or Granules for Oral Solution or Oral Suspension
Powder or granule formulations that require manipulation are
available in multiple forms including powder for oral solution,
powder for oral suspension, and granule for oral suspension.
Powder for Oral Solution
Epaned® (enalapril maleate) powder for oral solution from Sil-
vergate Pharmaceuticals, Inc., was approved in 2013 as a kit that
required manipulation and included a bottle of powder and a bottle of
Ora-Sweet diluent. Epaned® is indicated for the treatment of hyper-
tension with a dose of 0.08 mg/kg up to 5-mg once daily using a dose
volume 0.08 mL/kg of a 1 mg/mL reconstituted solution, which was
prepared by adding the 150 mL of diluent to the bottle of powder.
Epaned® (enalapril maleate) powder for oral solution was a formu-
lation containing mannitol and colloidal silicon dioxide. Epaned®
(enalapril maleate) powder for oral solution is being replaced by the
ready-to-use Epaned® (enalapril maleate) oral solution.
Firvanq™ (vancomycin HCl) powder for oral solution became
available in 2018 as kit from CurtisPharma that has a bottle of
powder for oral solution (150 mL or 300 mL) and a bottle of pre-
measured grape-flavored diluent. Vancomycin HCl is an antibac-
terial for the indication of clostridium difficileeassociated diarrhea
and enterocolitis caused by Staphylococcus aureus, including
methicillin-resistant strains. The amount of vancomycin HCl is 3.75
g, 7.5 g, or 15 g per bottle, and a bottle is constituted with 150 mL or
300 mL of the diluent to prepare an oral solution of 25 mg/mL or 50
mg/mL. The vancomycin HCl dose is 40 mg/kg t.i.d or q.i.d. for 7 to
10 days with the total daily dosage not exceeding 2 grams. The dose
volume of the 50 mg/mL suspension is 0.8 mL/kg t.i.d or q.i.d., or the
1.6 mL/kg, t.i.d or q.i.d. of the 25 mg/mL suspension. The Firvanq™
powder for oral solution formulation contains artificial grape flavor,
citric acid, D&C yellow no. 10, FD&C red no. 40, sodium benzoate,
sucralose, and water. To reconstitute Firvanq™ powder for oral
solution transfer about half the contents of the grape-flavored
diluent into the vancomycin hydrochloride powder bottle, shake
bottle vertically for approximately 45 s, add the remaining grape-
favored diluent, and shake the bottle for approximately 30 s. The
reconstituted solution is at 2 C-8 C, and discarded after 14 days, or
if it appears hazy or contains particulates.
Sabril® (vigabatrin) powder for oral solution from Lundbeck was
approved in 2016 for the treatment of infantile spasms. Sabril®
powder for oral solution is 500 mg of vigabatrin per packet and a
pack is constituted with 10 mL of water to a 50 mg/mL solution. The
initial daily dose is 50 mg/kg/d given in 2 divided doses (25 mg/kg
twice daily), and subsequent dosing can be titrated by 25 mg/kg/
d to 50 mg/kg/d increments every 3 days, up to a maximum of 150
mg/kg/d given in 2 divided doses (75 mg/kg twice daily). The
Sabril® (vigabatrin) powder for oral solution preservative-free
formulation contains only povidone as the inactive excipient. A
generic Vigabatrin for Oral Solution, 500 mg, became available in
2017 from Par Pharmaceuticals.
Powder for Oral Suspension
Promacta® (eltrombopag) for oral suspension from Glax-
oSmithKline was approved in 2015 for the treatment of thrombo-
cytopenia with a dose of 25 mg or 50 mg that is adjusted to
maintain za platelet count 50  109/L, using unit dose 25 mg
packets of a formulation containing mannitol, sucralose, and xan-
than gum. Promacta® for oral suspension is provided as a kit with
30 packets, 1 reusable bottle with lid and cap, and 1 reusable 20-mL
oral syringe. Promacta® for oral suspension is constituted with 20
mL of cold water and consumed immediately or within 30 min.
Nexium® (esomeprazole magnesium) for delayed-release oral
suspension from AstraZeneca was approved in 2007 for the treat-
ment of GERD with a once-daily dose of 10-40 mg using unit dose 10
mg, 20 mg, or 40 mg packets of a formulation containing the same
active enteric-coated granules (white to pale brown color) in the
capsules, along with inactive preservative-free granules (pale yel-
low color) containing dextrose, xanthan gum, crospovidone, citric
acid, iron oxide, and hydroxypropyl cellulose. Nexium® for delayed-
release oral suspension is constituted by adding the contents of a
packet to a catheter-tipped syringe; add 15 mL of water, shake, let
the suspension stand for 2-3 min to thicken, attach to a nasogastric
tube, and administer within 30 min. Alternatively, empty the con-
tents of a packet into a container with 15 mL of water, stir, let the
suspension stand for 2-3 min to thicken, and drink within 30 min.
Isentress® (raltegravir) powder for oral suspension from Merck
were approved in 2014 as an antiviral with a twice daily dose of 6
mg/kg/dose using a dose volume of 0.30 mL/kg of a 5 mg/mL
constituted suspension. Isentress® powder for oral suspension is
provided as a kit with each carton containing sixty 100 mg packets,
2 reusable mixing cups with lids, and 2 reusable 5-mL dosing sy-
ringes. Isentress® powder for oral suspension is a preservative-free
formulation containing ammonium hydroxide, banana with other
natural flavors, carboxymethylcellulose sodium, crospovidone,
ethylcellulose 20 cP, fructose, hydroxypropyl cellulose, hypro-
mellose 2910/6cP, PEG 400, magnesium stearate, maltodextrin,
mannitol, medium chain triglycerides, microcrystalline cellulose,
monoammonium glycyrrhizinate, oleic acid, sorbitol, sucralose, and
sucrose. Isentress® powder for oral suspension is constituted by
adding one 100 mg packet to the supplied mixing cup, add 5 mL of
water to prepare a 20 mg/mL suspension, cap the cup, mix, measure
the dose, and administer within 30 min.
Granules for Oral Suspension
Zmax® (azithromycin) granules for oral suspension from Pfizer
is an antibacterial with a dose of 60 mg/kg up to 2.0 grams using a
 R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365 1363

dose volume of 2.2 mL/kg (1 mL per pound body weight) of a 27
mg/mL constituted suspension, which is prepared by adding 60 mL
of water to a bottle with the granules. Zmax® is a single-use
package configuration of a prolonged-release preservative-free
formulation of lipid nanoparticles containing glyceryl behenate,
poloxamer 407, sucrose, sodium phosphate, magnesium hydroxide,
hydroxypropyl cellulose, xanthan gum, colloidal silicon dioxide,
titanium dioxide, artificial cherry flavor, and artificial banana flavor.
Prograf® granules (tacrolimus for oral suspension) from Astellas
Pharma is an immunosuppressant indicated for the prophylaxis of
organ rejection in patients receiving allogeneic liver, kidney, or
heart transplants with a twice daily dose of 0.075-0.15 mg/kg using
0.2 mg or 1.0 mg packets of a formulation containing cro-
scarmellose sodium, hypromellose and lactose monohydrate. Pro-
graf® granules (tacrolimus for oral suspension) are constituted by
adding the contents of a packet to 15-30 mL water, stir the sus-
pension, administer the suspension immediately, or the suspension
can be drawn up via a non-PVC oral syringe.
Protonix® (pantoprazole sodium) for delayed-release oral sus-
pension from Pfizer was approved in 2007 for the treatment of
erosive esophagitis associated with GERD and is packaged in unit
dose 40 mg packets. The dose is 20 mg (15-40 kg body weight) or 40
mg (>40 kg body weight) using a formulation containing crospo-
vidone, hypromellose, methacrylic acid copolymer, microcrystal-
line cellulose, polysorbate 80, povidone, sodium carbonate, sodium
lauryl sulfate, talc, titanium dioxide, triethyl citrate, and yellow
ferric oxide. Because proper pH is necessary for stability of pan-
toprazole, do not administer Protonix® for delayed-release oral
suspension in liquids other than apple juice, or foods other than
applesauce. To use applesauce, sprinkle granules on 1 teaspoonful
of applesauce. To use apple juice, empty granules into a small cup or
teaspoon containing 1 teaspoon of apple juice, stir for 5 s (granules
will not dissolve), and swallow immediately. To use a nasogastric
tube, empty the contents of the packet into the barrel of the sy-
ringe, add 10 mL (2 teaspoonfuls) of apple juice, and gently tap and
shake the barrel of the syringe to help rinse the syringe and tube.
Repeat at least twice more using the same amount of apple juice (10
mL or 2 teaspoonfuls) each time.
Tablets
Multiple types of manipulated tablets are available as pediatric
oral formulations including scored tablet, dispersible scored tablet,
and tablet for oral suspension. Note that the mini-tablets (oral
granules) that require manipulation are included in
multiparticulates.
Scored Tablets
Onfi® (clobazam) scored tablets from Lundbeck were approved
in 2011 for the treatment of seizure only with LGS with a dose of 5-
40 mg using a unit dose 10 mg or 20 mg scored tablet of a
preservative-free formulation containing corn starch, lactose
monohydrate, magnesium stearate, silicon dioxide, and talc. On
use, an intact Onfi® tablet or scored tablet is administered whole or
crushed and mixed with applesauce.
Siklos® (hydroxyurea) triple scored tablets from Addmedica was
approved in 2018 and is an antimetabolite, indicated to reduce the
frequency of painful crises and to reduce the need for blood trans-
fusions in pediatric patients, 2 years of age and older, with sickle cell
anemia with recurrent moderate-to-severe painful crises. The hy-
droxyurea once-daily dose is 15-30 mg/kg using 100 mg or triple
scored 1000 mg of a preservative-free formulation containing silic-
ified microcrystalline cellulose, sodium stearyl fumarate, and film-
coating agent amino methacrylate copolymer. The scored Siklos®
tablet can be administered whole, split, or dispersed immediately
before use in a small quantity of water in a teaspoon, and adding a
drop of syrup or mixing with food can mask a possible bitter taste.
Dispersible Scored Tablets
Coartem® (artemether and lumefantrine) dispersible scored tablet
from Novartis was approved in 2009 for the treatment of acute, un-
complicated malaria infections due to Plasmodium falciparum with a

Table 5
Excipients in New Oral Pediatric Formulations Marketed Since 2007

Taste Solid Formulations Solution and Suspension Formulations

Flavors Sweeteners Binders Capsule Shells Glidants Antifoam Solvents

Banana Acesulfame Hydroxypropyl cellulose Gelatin Silicon dioxide Simethicone Ethanol
Berry potassium Povidone Hydroxypropyl methylcellulose Talc Buffers and pH Glycerol
Cherry Ammonium Buffers and pH modifiers Coating Agents Lipids modifiers Propylene glycol
Grape glycyrrhizate Ammonium hydroxide Amino methacrylate Medium chain Acetic acid Sesame seed oil
Grapefruit Aspartame Calcium carbonate copolymer triglycerides Citric acid Water
Mixed berry Glucose Calcium hydrogen Basic butylated methacrylate Oleic acid Disodium Surfactants
Orange Maltitol phosphate copolymer Lubricants phosphate Poloxamer 188
Orange-vanilla Saccharin Citric acid Diacetylated monoglycerides Magnesium stearate Hydrochloric Polysorbate 80
Peppermint sodium Magnesium hydroxide Dibutyl sebacate Sodium stearyl fumarate acid Suspending and dispersing
Raspberry Sorbitol Sodium bicarbonate Ethylcellulose Polymers Sodium citrate agents
Strawberry Sucralose Sodium carbonate Glyceryl behenate Hypromellose Sodium Carboxymethylcellulose
Strawberry- Sucrose Sodium citrate Glyceryl monostearate Hypromellose acetate hydroxide sodium
vanilla Sodium phosphate Hypromellose phthalate succinate Dyes or colorant Hydroxyethyl cellulose
Tutti-frutti Tartaric acid Methacrylic acid copolymer PEG 400 FD&C Red Magnesium aluminum
Bulk agents and diluters Triethyl citrate Polyethylene oxide No. 40 silicate
Dextrose PEG 3350 Poly(vinyl alcohol) FD&C Yellow Microcrystalline
Erythritol Colorants Preservative No. 6 cellulose
Fructose Iron oxide Butylated hydroxytoluene D&C yellow Xanthan gum
Lactose Titanium dioxide Surfactants no. 10
Lactose monohydrate Disintegrants Poloxamer 188 Titanium dioxide
Mannitol Corn starch Poloxamer 407 Isotonicifier
Maltodextrin Croscarmellose sodium Polysorbate 80 Sodium chloride
Microcrystalline cellulose Crospovidone Sodium lauryl sulfate Preservatives
Silicified microcrystalline Pregelatinized starch Suspending and dispersing Benzyl alcohol
cellulose Sodium starch glycolate agents Methylparaben
Sucrose Carboxymethylcellulose Potassium sorbate
Sugar spheres sodium Propylparaben
Xanthan gum Sodium benzoate
1364 R.G. Strickley / Journal of Pharmaceutical Sciences 108 (2019) 1335-1365
twice daily dose of 1-3 tablets for 3 days of unit fixed-dose combi-
nation scored tablet with 20 mg artemether and 120 mg lumefantrine
of a preservative-free formulation containing colloidal silicon dioxide,
croscarmellose sodium, hypromellose, magnesium stearate, micro-
crystalline cellulose, and polysorbate 80. The scored Coartem® tablet
can be administered whole, split, or may be crushed and mixed with
1-2 teaspoons of water in a clean container.
Tablet for Oral Suspension
Tracleer® (bosentan) quadrisected tablet for oral suspension from
Actelion Pharmaceuticals US was approved in 2017 for the treatment
of pulmonary arterial hypertension with a twice daily dose of 16, 32,
48, or 64 mg using a quadrisected tablet of total unit dose 32 mg of a
preservative-free formulation containing microcrystalline cellulose,
calcium hydrogen phosphate, croscarmellose sodium, silica colloidal,
tartaric acid, tutti-frutti flavor, aspartame, acesulfame potassium, and
magnesium stearate. The quadrisected tablets are packaged in blisters
and on use an intact tablet or scored tablet is dispersed in a minimal
amount of water immediately before administration.
Carbaglu® (carglumic acid) triple-scored tablet for oral suspen-
sion from Recordati Rare Diseases was approved in 2010 for the
treatment of chronic hyperammonemia due to deficiency of the
hepatic enzyme N-acetylglutamate synthase with a dose 100-250
mg/kg/d divided into 2 or 4 doses using a triple scored 200 mg
tablet of a preservative-free formulation of croscarmellose sodium,
hypromellose, microcrystalline cellulose, silica colloidal anhydrous,
sodium lauryl sulfate, and sodium stearyl fumarate. An intact Car-
baglu® tablet or scored tablet is constituted in a small cup with 2.5
mL of water per tablet and stirred and administered as a drink
through a syringe or nasogastric tube.
Afinitor® Disperz™ (everolimus) tablet for oral suspension from
Novartis was approved in 2012 for the treatment of tuberous
sclerosis complexeassociated partial-onset seizures with a dose
of 5 mg/kg2 or adjusted to attain trough plasma concentrations of
5-15 ng/mL. The dose is adjusted by the number of 2 mg, 3 mg, and
5 mg unit dose tablets of a preservative-free formulation of butyl-
ated hydroxytoluene, colloidal silicon dioxide, crospovidone,
hypromellose, lactose monohydrate, magnesium stearate,
mannitol, and microcrystalline cellulose. Afinitor® Disperz™ tablets
for oral suspension are packaged in blisters and on use, the tablets
are constituted by adding the tablets to a syringe, and water is
pulled into the syringe, the contents are mixed to a suspension, let
stand for 3 min, and the syringe is gently inverted 5 times imme-
diately before administration. Afinitor® Disperz™ tablet for oral
suspension must be dispersed in water, not swallowed whole,
chewed, or crushed.
Cozaar® (losartan potassium) tablet for oral suspension from
Merck is for the treatment of hypertension with a dose of 0.7 mg/kg
up to 50 mg total using a dose volume of 0.28 mL/kg, a 2.5 mg/mL
constituted suspension. Cozaar® tablet for oral suspension is sup-
plied as 25 mg, 50 mg (scored), or 100 mg tablets of a preservative-
free formulation containing microcrystalline cellulose, lactose,
pregelatinized starch, magnesium stearate, hydroxypropyl cellu-
lose, hypromellose, and titanium dioxide. Cozaar® tablet for oral
suspension is constituted by adding 10 mL water to a 240-mL PET
bottle; add ten 50 mg tablets, shake for 2 min, let stand 1 h, shake
1 min, add 190 of a 50/50 mixture of Ora-Plus and Ora-Sweet, shake
for 1 min, then administer. The constituted Cozaar® suspension can
be stored at 2 C-8 C for 4 weeks. In December 2015, Camber
Pharmaceuticals announced generic losartan potassium tablets.40
EMFLAZA™ (deflazacort, prodrug of corticosteroid, 21-desDFZ)
tablet for oral suspension originally developed by Marathon Phar-
maceuticals, LLC was approved in 2018 for the treatment of
Duchenne muscular dystrophy with a dose of 0.9 mg/kg rounded
up to the nearest possible dose using unit dose tablets of 6 mg, 18
mg, 30 mg, or 36 mg of a formulation containing colloidal silicon
dioxide, lactose monohydrate, magnesium stearate, and pregelati-
nized corn starch. On use, an intact EMFLAZA™ tablet is adminis-
tered whole or crushed and mixed with applesauce.
Excipients in Oral Pediatric Formulations
Table 5 lists the excipients that are in the oral pediatric formu-
lations in Tables 3 and 4. Table 5 is divided into 3 categories: taste,
solid formulations, and solution and suspension formulations.
Within the 3 categories are the excipient functions in the alpha-
betical order.
Conclusion
Current trends and recent advances suggest that the future of
pediatric oral formulations is with single-use, preservative-free,
taste-masked, solid dosage forms including mini-tablets, ODTs,
chewable tablets, scored tablets, granules and powders, and tablets
for oral solution or suspension, and a variety of multiparticulates
including sprinkle capsules, oral powders, oral granules, and
manipulated mini-tablets. These solid oral pediatric formulations
are packaged in various configurations including conventional
bottles, sachets, stick packets, blisters, or 2-piece capsules. It is the
author’s opinion that the use of mini-tablets will likely increase and
may include moving toward uncoated 2-mm mini-tablets admin-
istered individually to children as young as 2 days of age.
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