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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JAGANI et al

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: c.tuleu@ucl.ac.uk

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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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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