Can a Flavored Spray (Pill Glide) Help Children Swallow Their Medicines? A Pilot StudyMamta Jagani, MPharm, a Hélène Legay, PharmD, a, b, c Sejal R Ranmal, MPharm, PhD, b Julie Bertrand, PhD, d, e Kuan Ooi, MPharm, a Catherine Tuleu, PharmD, PhDb
aGreat Ormond Street Hospital for Children National
Health Service Foundation Trust, London, United Kingdom; bSchool of Pharmacy, and dUCL Genetics Institute, University
College London, London, United Kingdom; cCamden and
Islington National Health Service Foundation Trust, London,
United Kingdom; and eUnité Mixte de Recherche 1137,
Institut National de la Santé et de la Recherche Médicale,
Université Paris Diderot, Paris, France
Ms Jagani conceptualized and designed the
study, coordinated, assisted and supervised data
collection, drafted the initial manuscript, and
reviewed and revised the subsequent manuscript
drafts until completion; Dr Legay coordinated
study documentation, assisted in data collection,
and critically reviewed and revised the various
manuscript drafts until completion; Dr Ranmal
contributed to the design of the data collection
instruments, drafted the application for research
ethics committee approval, and reviewed and
revised the manuscript; Dr Bertrand undertook the
statistical analysis and reviewed and revised the
various manuscript drafts; Ms Ooi substantially
contributed to the conception and design of the
study and critically reviewed the fi nal draft of the
manuscript; Dr Tuleu was the principal investigator,
designed the study, obtained the research and
development and research ethics committee
approvals, carried out the initial analyses, and
reviewed and revised the subsequent manuscript
drafts until completion; and all authors approved
the fi nal manuscript as submitted and agree to be
accountable for all aspects of the work.
DOI: 10.1542/peds.2016-0680
Accepted for publication Aug 22, 2016
Swallowing difficulties affect
people of all ages, but may be more
prevalent in children, with many
unable or unwilling to swallow
conventional tablets or capsules.
Issues with palatability, storage,
stability, and costs often occur
where liquid alternatives exist.
Acceptability of medicines 1 is likely
to have a significant impact on
patient adherence, and consequently
safety and efficacy. Size and shape
are critical acceptability attributes
for monolithic dosage forms to be
swallowed intact; however, the need
for training or dosing aids should also
be considered. 2 A recent systematic
review detailed various swallowing
interventions, including behavioral
therapy, a flavored spray (Pill Glide),
specialized cups, and head posture
training. 3 All were successful in their
own right, but studies were limited
by their observational nature, small
sample size, and lack of controls,
highlighting the pressing need for
additional research.
Pill Glide (Conformité Européenne-
approved medical device) is a flavored
swallowing spray. Encouraging
testimonials 4 claim that it significantly
abstractPediatric pharmacists are constantly faced with the challenges of
supporting children and caregivers for whom the difficulties of swallowing
medicines can be a daily struggle. Most medicines are only available as
tablets and capsules, and where liquid alternatives exist, these products
often have issues with palatability and high costs. The objective of this
study was to evaluate whether the swallowing spray, Pill Glide, could help
children in taking their solid and liquid medicines. This open label pilot
study compared the spray with a behavioral approach alone, the current
standard of care at the pediatric hospital. Patients were children on long-
term drug therapies, either transitioning from liquid preparations to tablets
and capsules, or known to be experiencing swallowing difficulties. Using
age-adapted diaries, patients self-reported the difficulty of taking medicines
on a 6-point hedonic scale for 2 weeks before the intervention, and then
for 1 week while using Pill Glide. Data were analyzed from 10 children
aged 6 to 16 years, with an average burden of 3.5 tablets per day. Pill Glide
(strawberry was the most popular flavor) was shown to significantly
decrease the overall medicine taking difficulty score by 0.93 (range,
0.33–1.53), almost 1 hedonic face point on the scale used (P = .002). There
was insufficient data for liquid medicines. Pill Glide could help children
with pill swallowing, thus improving patient acceptability of medicines and
potentially adherence. It could also be implemented as a useful cost-saving
intervention because solid dosage forms are cheaper.
CASE REPORTPEDIATRICS Volume 138 , number 6 , December 2016 :e 20160680
To cite: Jagani M, Legay H, Ranmal SR, et al. Can a
Flavored Spray (Pill Glide) Help Children Swallow
Their Medicines? A Pilot Study. Pediatrics. 2016;
138(6):e20160680
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JAGANI et al
helps people to swallow medicines.
In 1 uncontrolled study, 7 out of 11
teenagers (aged 9–17 years) with
self-reported swallowing difficulties
successfully took 1 tic-tac candy
(∼8 mm in size) using Pill Glide. 5
However, no prospective, controlled
studies with younger children have
been published. This study was
prompted by anecdotal evidence
(M. J., personal communication, 2009),
whereby Pill Glide helped a young
patient with HIV at Great Ormond
Street Hospital for Children (GOSH),
leading to significant improvement
in viral load. To improve adherence
and quality of care, this pilot study
objectively compared Pill Glide
with the current GOSH behavioral
approach based on information
leaflets to support parents/
caregivers in the administration of
medicines to children. Furthermore,
Pill Glide could be resource effective
for healthcare providers because
evidence suggests that switching
from oral liquids to solid dosage
forms could lead to considerable cost
savings. 6
CASE REPORT
This open label study ( Fig 1) was
approved by a National Health
Service research ethics committee
(REC) (REC number 11/LO/0831).
Over 3 weeks, patients used age-
adapted, self-reporting diaries to
record difficulty/ease of swallowing
their medicines, using a 6-point
numeric or facial hedonic scale,
ranging from 0 “not difficult”
(happiest face) to 5 “most difficult”
(saddest face). For the first 2 control
weeks, baseline data were recorded
while implementing the GOSH
behavioral training package. 7 For
the third week, patients used the Pill
Glide sprays (grape, orange, peach,
or strawberry flavors, courtesy
of FLAVORx, Inc). Patients were
instructed to spray once before and
once after taking each dose of every
medication. For patients taking liquid
medications, taste improvement was
recorded as a secondary outcome,
as was flavor preference. A 2-week
baseline measurement and a
1-week intervention period were
recommended to avoid bias and
placebo effect. All study material,
including diaries, information
sheets, and consent/assent forms,
were reviewed for age and cognitive
appropriateness by members of the
Young People’s Advisory Groups of
the Medicines for Children Research
Network.
Participants were children on
multiple drug therapies and children
transitioning from liquid to solid
medicines; patients were recruited
from the bone marrow transplant
and infectious diseases wards and
HIV out-patient settings. Children
were excluded if they had any known
swallowing impairment, or food or
e2
FIGURE 1Flowchart of the Pill Glide study. PIL, patient information leafl et.
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PEDIATRICS Volume 138 , number 6 , December 2016 e3
FIGURE 2AGender, age and medicines (including sizes and shapes of solid dosage forms) taken by patients in the Pill Glide study. The asterisk indicates information is missing and the size of capsules have been estimated. API, active pharmaceutical ingredient; BD, twice daily; e/c, enteric coated; OD, once daily. (continued)
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JAGANI et al e4
FIGURE 2BGender, age and medicines (including sizes and shapes of solid dosage forms) taken by patients in the Pill Glide study. (continued)
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PEDIATRICS Volume 138 , number 6 , December 2016 e5
FIGURE 2CGender, age and medicines (including sizes and shapes of solid dosage forms) taken by patients in the Pill Glide study. (continued)
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drug allergies. A total of 25 children
aged 6 to 17 years were enrolled
after 11 months, mostly from the HIV
outpatient clinic, but only 10 fully
completed diaries were returned
(response rate, 40%). The average
age of participants (60% girls) was
12.3 years (median, 13 years, range,
6–16 years). The size and shape of
solid dosage forms varied widely but
the burden of administration was
relatively high for most patients ( Figs
2A, 2B, 2C, and 2D). Participants took
a total of 15 nonmanipulated solid
and 3 liquid forms, with the number
of medicines per child averaging
3.5 tablets per day.
For each patient (i = 1, ..., 10) and
prescribed drug (k = 1, ..., nik; eg,
for patient F13, nik = 4), an overall
Medicine Taking Difficulty Score
(MTDSik) was calculated as the
sum of the reported scores at
each administration (d) of the
drug (MTDSikd) divided by the
corresponding total number of
administrations (nDik) taken over a
given period:
MTD S ik = ∑ d=1 n Dik MTD S ikd
_______________ n Dik
This MTDS (from 0–5) was calculated
for both the behavioral and Pill Glide
periods, with score values for each
period compared in pairs as defined
by the indexes i and k.
Figure 3 illustrates MTDS for the 2
periods for each participant, for all
dosage forms and for solid dosage
forms only. A subject had as many
score estimates as drugs taken.
Overall, the results were excellent
for solid medications, for which the
strawberry spray was used most
frequently. The mean difference in
overall MTDS between the behavioral
approach and Pill Glide intervention
periods ( Fig 4) was 0.93 (range, 0.33–
1.53), almost 1 hedonic face point on
the scale. This decrease with Pill Glide
was statistically significant (P = .002,
paired t test, 24 degrees of freedom).
Only 1 patient (a 6-year-old taking
lamivudine solution) had an increased
score of >1 point with Pill Glide.
Exposure to Pill Glide excipients was
minimal and deemed safe. There were
no reports of acute reactions nor
adverse events or choking episodes
at enrollment and during the study
period . In contrast, some very
positive comments were received; for
example, “The tablet just slid down my
throat;” “I don’t have to cut my tablets
in half anymore;” “I never thought I
could swallow whole tablets.”
DISCUSSION
These results support the use of Pill
Glide in children, because it aided their
ability to swallow relatively large,
solid oral dosage forms and avoided
the need for manipulations. This is a
widespread practice in pediatrics and
e6
FIGURE 2DGender, age and medicines (including sizes and shapes of solid dosage forms) taken by patients in the Pill Glide study.
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PEDIATRICS Volume 138 , number 6 , December 2016
can have detrimental consequences
on safety and efficacy. For example,
the unpleasant Kaletra (lopinavir/
ritonavir) oral solution is poorly
accepted by children; it has a high
ethanol (42.4% vol/vol) and propylene
glycol content (15.3% wt/vol). 8, 9 If
swallowing whole is not feasible,
the alternative is either breaking or
crushing the tablet. This has been
shown to significantly reduce drug
exposure, with area under the curve
halved 10 and patients potentially
requiring higher doses and therapeutic
drug monitoring. Although such
manipulation should be avoided,
patients and their caregivers are often
left with very few alternative options.
In the current study, 2 participants
reported that they stopped halving
their efavirenz tablets by the fifth day
of using Pill Glide, whereas another
6-year-old participant successfully
transitioned from liquid to tablet
formulation.
Efforts have been made in recent
years to try to establish a relationship
between acceptable tablet and
capsule sizes/shape and the age of
children, 11, 12 but the evidence behind
prescriptive limits is lacking, 13
and numerous other factors (eg,
indication, patient and caregiver
motivation, and counseling from
healthcare professionals) are equally
important. 14 One-third of adults also
reportedly suffer from difficulties
swallowing medicines.15 Therefore, a
positive, self-implementing strategy,
such as Pill Glide, could have wider
benefits. This study demonstrated the
ease and resource effectiveness of this
intervention (excluding the cost of the
device), which is not disease-specific
and is applicable to different/any
solid dosage forms. Tablet crushers
are often provided to patients, so Pill
Glide could simply be another medical
device supplied to aid administration
and improve therapeutic outcomes.
The National Health Service
recognizes the importance of offering
patients the opportunity to be more
involved and make choices regarding
their treatment. 16 Pill Glide provided
children with some control and
autonomy in taking their medicines
(for which they have no choice) with
the additional choice of 4 flavors (to
avoid aversion or monotony). This
empowering and positive experience
may have additionally assisted with
successful pill swallowing.
The small number of patients
recruited for this pilot study was
just above the recommendations for
improved quality of evidence. 3 Fifteen
patients did not return all diaries,
some because of the cumbersome
nature of completing them, whereas
others disliked having the diaries
around the house because of the
stigma associated with taking HIV
medicines. The study could have
been extended to other specialties,
such as cardiac or renal transplant
patients, who are also prescribed
relatively large tablets long-term
(eg, mycophenolate and tacrolimus),
and for which therapeutic levels can
e7
FIGURE 3Overall MTDS for the behavioral and Pill Glide periods. A, Scores for each subject and all dosage forms. B, Scores for only the solid dosage forms. Paired scores were linked together by a solid line if the score was lower for Pill Glide and a dashed line if the score was higher.
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JAGANI et al
be monitored. However, monitoring
clinical parameters would have
required additional REC scrutiny and
was not included for the purposes
of this unfunded pilot study. During
REC review, the need for an extra
control group using water or another
nonflavored spray was proposed.
However, considering both clinical
issues (absence of an aid in practice)
and ethical issues (potential negative
discrimination in this arm), it was
concluded that patients would act
as their own control for a baseline
measurement period. This is in
line with recommendations for
improved quality of evidence, 3 with
the advantage of fewer confounding
factors and the need for fewer
participants to detect a relevant score
difference.
It was not possible to determine from
the current study whether the spray
could mask the unpleasant taste or
aftertaste of liquid medicines. This
apparent negative effect was only
based on data for 2 patients and 3
preparations that were unlikely to have
palatability issues (medium scores).
However, it helped some patients
transition to solid medications.
Additional research incorporating
more patients and unpalatable liquids
is required to draw appropriate
conclusions. Similarly, different patient
characteristics (eg, age and gender)
and formulation attributes (eg, size
and shape) could be explored in a
larger study.
CONCLUSIONS
The present pilot study demonstrated
that Pill Glide is safe, easy, and effective
to help children ≥6 years of age to
take their solid medicines compared
with a standard behavioral approach
alone. It is recommended that Pill
Glide be widely available, given the
current paucity of age-appropriate
dosage forms for children. A larger
study is warranted to further examine
these findings over a longer time
period, which may be additionally
strengthened by including measurable
clinical compliance markers.
Establishing any pharmacoeconomic
impact may also highlight such
interventions to be a cost-effective
solution for healthcare providers.
ACKNOWLEDGMENTS
We thank the Medicines for Children
Research Network Young People’s
Advisory Groups for their input. We
also thank all the families for their
participation.
e8
ABBREVIATIONS
GOSH: Great Ormond Street
Hospital
MTDS: Medicine Taking Difficulty
Score
REC: Research Ethics Committee
FIGURE 4Overall MTDS average trend lines for the baseline behavioral approach and Pill Glide intervention periods grouped by dosage form type.
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PEDIATRICS Volume 138 , number 6 , December 2016
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e9
Address correspondence to Catherine Tuleu, PharmD, PhD, Department of Pharmaceutics, University College London School of Pharmacy, 29–39 Brunswick
Square, London WC1N 1AX, United Kingdom. E-mail: [email protected]
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2016 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: Pill Glide sprays were donated by FLAVORx, Inc. The authors have indicated they have no other fi nancial relationships relevant to this
article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential confl icts of interest to disclose.
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DOI: 10.1542/peds.2016-0680 originally published online November 1, 2016; 2016;138;Pediatrics
Catherine TuleuMamta Jagani, Hélène Legay, Sejal R Ranmal, Julie Bertrand, Kuan Ooi and
Pilot StudyCan a Flavored Spray (Pill Glide) Help Children Swallow Their Medicines? A
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DOI: 10.1542/peds.2016-0680 originally published online November 1, 2016; 2016;138;Pediatrics
Catherine TuleuMamta Jagani, Hélène Legay, Sejal R Ranmal, Julie Bertrand, Kuan Ooi and
Pilot StudyCan a Flavored Spray (Pill Glide) Help Children Swallow Their Medicines? A
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