Pediatric 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.
- GOSH —
- Great Ormond Street Hospital
- MTDS —
- Medicine Taking Difficulty Score
- REC —
- Research Ethics Committee
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 medicines1 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 testimonials4 claim that it significantly 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
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 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:
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.”
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 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 halved10 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 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.
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.
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.
- Accepted August 22, 2016.
- 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:
FINANCIAL DISCLOSURE: Pill Glide sprays were donated by FLAVORx, Inc. The authors have indicated they have no other financial relationships relevant to this article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
- European Medicines Agency
- Committee for Medicinal Products for Human Use
- Patel A,
- Jacobsen L,
- Jhaveri R,
- Bradford KK
- Diamond S,
- Lavallee DC
- Lajoinie A,
- Henin E,
- Kassai B,
- Terry D
- Great Ormond Street Hospital for Children NHS Foundation Trust
- Electronic Medicines Compendium
- European Medicines Agency; Committee for Medicinal Products for Human Use
- UK Department of Health
- Copyright © 2016 by the American Academy of Pediatrics