Basic matters related to the method of dispensing oral-dose liquid medication and other pre-scription drugs in Japan have been set forth in the Dispensing Guidance issued by the Japan Pharmaceutical Association. However, accurate ways of dispensing vary among medical facilities and pharmacies. In case of oral-dose liquid medication such as antipyretics and expectorants often used for pediatric patients, the pharmacists often subdivide the liquid from a 500-mL glass container into smaller plastic containers and provides the subdivided liquid after dilution in a volume needed for a given patient. The present study was undertaken to evaluate the ease of use of several kinds of liquid medication containers and measuring devices during experimental measuring of phantom drug solution. The study was additionally designed to evaluate the extent of knowledge about the Child Resistance (CR) caps, and the ease or difficulty in removing such a cap. The collaborators to this study attached importance to the accuracy in measuring the liquid, the ease of reading the graduations and the design allowing hygienic handling as the factors determining the most easily usable liquid medication containers. The results additionally show that the recognition of the CR cap among people is not high at present.

Keywords: liquid medication, pediatric, plastic container, child resistance (CR), administration, device

In Japan, liquid medication containers are routinely used in clinical practices. Medical facilities and pharmacies often handle liquid medication containers used for oral-dose liquid medication, used for prevention and treatment of illnesses, and topical-dose liquid medication (disinfectants for prevention of infection).

Oral-dose liquid medication allows flexible dose level adjustment and this formulation of medication has been most frequently adopted for pediatric oral medication in Western countries.^1-3 In Japan, on the other hand, powder is a frequently used formulation of medication for children. During the neonatal and infantile periods, powdered medication is dissolved or suspended in water immediately before oral administration.¹ In Japan, medical care for symptoms, such as a cold and allergy, is also covered by the national health insurance (NHI), and drugs, such as antipyretics, antitussives, expectorants and adrenocortical steroids, are prescribed for patients complaining of such symptoms, with the costs covered by the NHI. Furthermore, in many local communities, the healthcare expenses for children before graduation from junior high school, or before graduation from senior high school in some local communities, covered by public funds. Those complaining of symptoms of a cold or allergy often visit general practitioners as outpatients. For children from the pre-school age to low grades of elementary school, the antipyretics, antitussives, expectorants, and adrenocortical steroids are often prescribed in the form of oral-dose liquid medication, which allow easier dose level adjustment, rather than powdered medication.

Basic matters related to the method of dispensing oral-dose liquid medication and other prescription drugs in Japan have been set forth in the Dispensing Guidance issued by the Japan Pharmaceutical Association. However, accurate ways of dispensing vary among medical facilities and pharmacies. In case of oral-dose liquid medication such as antipyretics and expectorants often used for pediatric patients, the pharmacists often subdivide the liquid from a 500-mL glass container into smaller plastic containers and provides the subdivided liquid after dilution in a volume needed for a given patient. In Japan, the oral-dose liquid medication is orally taken by roughly two methods: (1) the volume to be taken per dose (mL) is shown to the patient or his/her family, accompanied by instructions to measure this volume of the liquid with a cup or spuit (syringe); and (2) the dispensing pharmacist adds water to the liquid medication container up to the printed or embossed indicator line, followed by giving an instruction to the patient or his/her family to measure the liquid in a volume equivalent to one scale marked on the container (= volume to be taken per dose). Concerning syrup preparations, it has been reported that 66.4% of the facilities in Japan are providing syrup preparations after dilution corresponding to the graduations marked on the liquid medication container,⁴ indicating that the widely adopted method of measuring oral-dose liquid medication in Japan is the one using the graduations marked on the liquid medication containers. Under the NHI healthcare service reimbursement system in Japan, there is a provision: “The drug containers used for medication are lent from the NHI-covered medical facilities to patients, as a rule. If they desire, they can purchase the container at the actual cost. However, if they have returned the container concerned and the main part of it can be re-used, the cost paid for the container needs to be refunded.”⁵ In this connection, a notification issued in the past from the Ministry of Health and Welfare (currently the Ministry of Health, Labour and Welfare) states: “If a reusable container, regardless of its material, has been returned by the patient, the NHI-covered medical facility (including the NHI-covered pharmacy) is required to refund the container’s cost having been collected from the patient at the time of its return. It is not acceptable to collect the cost of the non-reusable container from the patient when the container is given to the patient.”⁶ At present, the actual cost of the plastic liquid medication container can be billed to the patient only when the patient explicitly desires the container and, even when the patient desires the container, the medical facility or pharmacy often avoids billing the container’s cost for the reason of procedural complexity or within the framework of patient services. It is plausible to imagine that many of the NHI-covered medical facilities and pharmacies, which do not bill the cost of the containers given to patients, are selecting the containers to be adopted through laying more emphasis on the price of the containers from wholesalers than on the usability or functionality of the containers. However, the usability and functionality of containers are closely related to the probability for accurate measurement of the liquid medication and hence associated with under- and over-doses of liquid medication through erroneous measuring. In Japan, no definite guidelines are available concerning not only liquid medication containers but also the measurement scales on the containers (e.g., cup and spuit), and the judgment about them has been assigned to NHI-covered medical facilities and pharmacies. It is unknown whether the measurement scales on the liquid medication containers are appropriate ones and are easy to use by parents, guardians or children.⁷

It has been reported that the incidence of erroneous drug administration to children by parents or guardians was much higher with the use of cups than with the use of spuits, spoons or syringes⁸ and that many of the preventable adverse events related to medication in pediatric outpatients were often attributable to erroneous drug administration.⁹ Furthermore, errors in administering liquid medication to children by parents or guardians have been occurring frequently, and it has been suggested that the practice of measuring the liquid with the use of a syringe and educational intervention for guardians are useful in reducing errors in liquid medication administration.¹⁰ Although the circumstances surrounding the selection of liquid medication containers and measuring devices differ greatly between Japan and other countries, there are few published report concerning evaluation of the usability of different forms of liquid medication containers when used for the liquid medication dosing practice specific to Japan, i.e., the practice of adding water to the liquid medication container up to the printed or embossed indicator line at the pharmacy, followed by giving instructions to the patient or his/her family to orally take the liquid in a volume equivalent to one scale of the graduations marked on the container (= volume to be taken per dose).

The present study was undertaken to evaluate the ease of use of several kinds of liquid medication containers and measuring devices during experimental measuring of phantom drug solution by male and female adults having experienced with measuring liquid medication for their children before. The study was additionally designed to evaluate the extent of knowledge about the CR (child resistance) caps, a CR cap relatively unfamiliar in Japan, and the ease or difficulty in removing such a cap.

Study design

Collaborators for this study were recruited from inhabitants at Izumi Ward and Totsuka Ward of Yokohama City. Each collaborator was asked to open the cap of each liquid medication container (Containers A through D) and to record the time taken for measuring the liquid from the container into the cup in a volume equivalent to a single dose (one scale). After the liquid was added to the cup, the collaborator was asked to fill in the questionnaire. In addition, a questionnaire survey was conducted also concerning the CR cap opening time and the awareness about CR caps. In cases where the CR cap could not be opened in 30 seconds, explanation was given with the use of a leaflet attached to the CR cap and the time taken for opening the CR was recorded again.

Study population

This observational study of liquid medication containers and measuring devices was carried out by the Yokohama University of Pharmacy. The survey involved the individuals who, as guardians for their children, had experienced with measuring liquids from liquid medication containers to administer them to their children.

Liquid medication containers, measurement scale, and drug solution

Containers A through F were liquid medication containers (30 mL) of the same manufacturer. The drug solution tested was simple syrup JP (Kenei Pharmaceutical Co., Ltd., Osaka City, Osaka Prefecture, Japan). Of all test containers, only Containers A through D were used for measuring the liquid. In case of Containers A and B, the collaborator removed the cap, and the liquid was poured directly from the container into the cup in a volume equivalent to one scale. In case of Container C, the liquid was added to the cup with the use of a measuring spuit. In case of Container D, the liquid was poured the cup with the use of spuit integrated with the cap. Container A was the same as Container C, both having the same cap, but the way of measuring the liquid differed between these containers (Container A: direct measurement, Container C: measurement with the attached spuit).

Collaborators were told in advance that if an excess volume of the liquid has been added to the cup, the excess liquid may be returned to the container at their own discretion (they were told that if they used to decide returning the excess liquid from the cup into the container during their past attempts of administering liquid medication to their children, they are permitted to do such a returning procedure also in this study). Container D had a cap that was the same as that of Containers A and C except that the cap of Container D was integrated with the spuit. Container E had embossed graduations and was used only for the questionnaire survey. Container F was the same as Container E except for the cap design (the CR cap was adopted for Container F), and each collaborator actually performed the cap-opening test with this container (Figure 1, Table 1,2).

Figure 1 Liquid medication containers and measurement scale used.
(I) Containers used (A-D: Each collaborator measured the liquid using the cup shown in front of the container in a volume equivalent to one scale of graduation; C: Measured into the cup using the spuit shown in front of the container) ; (II) Each collaborator measured the liquid in a volume equivalent to one scale of graduations from the container filled with the liquid in a volume equivalent to 3 scales of graduations marked with the arrow. ; (III) Container B’s nozzle and cap; (IV) CR cap; (V) (Lower): Spuit for use in measuring from Container C, (Upper): Spuit integrated with the cap for Container D.

Questionnaire

Table 2 shows the contents of the questionnaire.

Survey period

The survey was conducted between November 2022 and January 2023.

Data analysis

Statistical analysis employed JMP ver.14.3.0 (SAS Institute Inc.).

Ethical review

This study was started after having been reviewed and approved by the Yokohama University of Pharmacy Clinical Study Ethics Committee (“Protocol # C22002A” as per the updated guidelines of the Declaration of Helsinki (64th WMA General Assembly, Fortaleza, Brazil, October 2013). Informed consent was obtained in writing from each collaborator prior to the study.

Collaborators

During this study, evaluation was made by 40 collaborators. Of all collaborators, 90.0% (36) were female and 10.0% (4) were male. Their median age was 45 (IQR: 41.3-49.0). The median pinching power of the dominant hand of collaborators was 13.3 kg (IQR: 11.1-17.0).

Parameters of measuring the liquid from liquid medication containers

Time taken for measuring

The median time spent by collaborators for measuring the liquid from liquid medication containers was 22 seconds (IQR: 19.25-28) for Container A, 28.5 seconds (IQR: 21-40) for Container B, 34 seconds (IQR: 29-39.75) for Container C and 33.5 seconds (IQR: 25-45) for Container D. There was no correlation between the age of collaborators and the time spent for measuring the liquid from each container or between the pinching power and the time spent for measuring the liquid from each container (Table 3).

Other parameters

Of the 40 collaborators, 4 spilled the liquid during the measuring procedure. There was no collaborator who spilled the liquid from two or more containers. Spilling occurred during measuring from Container C by 3 collaborators and from Container D by one collaborator. Of the 40 collaborators, 10 returned the excess measured liquid into the container. There was no collaborator who returned the excess measured liquid into two or more containers. Returning of the excess measured liquid was done into Container C by 6 collaborators, into Container D by 3 collaborators and into Container A by one collaborator.

Usability of Containers A through D

Figure 2 shows the results of liquid medication container usability evaluated by the collaborators. In evaluation of “ease of measuring the liquid,” the median numeric rating scale (NRS) score was highest (7.5) with Container C, followed by Container D (7), Container B (6) and Container A (5). This score differed significantly between Container A and B, between Container A and C, and between Container A and D. In evaluation of “ease of cap opening/closing,” the median NRS score was highest with Container A and B (6.5), followed by Container D (6) and Container C (5.5). This score did not differ significantly between any two of the containers. To the inquiry “Do you think this is a container allowing hygienic handling?”, the median NRS score was highest with Container D (8), followed by Container B (7), Container A (5) and Container C (4.3). This score differed significantly between Container A and D, between Container B and C, and between Container C and D (Figure 2). Table 4 gives the free comments of collaborators about each container. On each container, positive, negative and correction-requesting comments were given.

Figure 2 Evaluation of usability of liquid medication containers.
Median score of Container A in evaluation of “ease of measuring the liquid” is 5 (n=40, Steel-Dwass test **P<0.01, *P<0.05).

Most easily usable container among Containers A through D (comprehensive evaluation of the shape, manipulability and easy to measure of the container and the measurement scale)

All of the 40 collaborators answered the question about the most easily usable container. Container B was answered most frequently (40.0%, 16 collaborators), followed by Container D (37.5%, 15 collaborators), Container C (12.5%, 5 collaborators) and Container A (10.0%, 4 collaborators). Thus, 77.5% of all collaborators selected Container B or D as the most easily usable container. In this procedure during which each collaborator was asked to select one out of the Containers A though D as “the most easily usable container,” there was no significant difference in the representative value of age or pinching power between any two of the collaborator groups having selected each container (A, B, C or D) (Kruskal-Wallis test: age p=0.14, pinching power p=0.59).

Table 5 shows the free comments about “the most easily usable container” selected by individual collaborators.

Table 6 shows the coefficient of correlation of age and pinching power with each parameter of the liquid medication containers (ease of measuring the liquid, ease of cap opening/closing, and hygienic design). For Container D, a weak negative correlation was noted between age and ease of cap opening/closing.

More desirable graduations

When Container A (printed graduations) was compared with Container E (embossed graduations), 90.0% (36 collaborators) selected Container A as more desirable, 7.5% (3 collaborators) selected Container E as more desirable, and 2.5% (1 collaborator) made a neutral answer (both acceptable). Comments given to Container A included “colored graduations are easily visible” (32 collaborators), “visible without relying on illumination” (28 collaborators) and “ease of visualization is unlikely to be affected by the features of the liquid contained” (2 collaborators). Comments to Container E included “graduations likely to be read erroneously when busy” (5 collaborators), “graduations are not visible by elderly people” (5 collaborators), “want to judge the graduations by pressing the surface with nail” (1 collaborator) and “no fear of disappearance of graduations” (1 collaborator).

More desirable spuit

When Container C (with a spuit provided separately) was compared with Container D (with a spuit integrated with the cap), 60.0% (24 collaborators) selected Container D as more desirable and 37.5% (15 collaborators) selected Container C as more desirable. The remaining 2.5% (1 collaborator) made a neutral answer (both acceptable).

Comments given to Container C included “not affected by the drug volume because the spuit can reach the bottom” (6 collaborators), “easy to measure” (6 collaborators), “easy to manipulate” (3 collaborators), “no need of declining the container” (1 collaborator) and “hygienic” (1 collaborator). Comments given to Container D included “no trouble in finding a place for storage after use” (17 collaborators), “hygienic” (17 collaborators), “no need to wash” (3 collaborators), “no fear of losing” (3 collaborators) and “easy to measure” (1 collaborator).

Containers handled before

Collaborators were asked to answer about the containers they had handled before among Containers A through E, allowing them to make multiple answers. Container A were answered by the largest number of collaborators (39/40, 98%), followed by Container C (20/40, 50%), Container B (8/40, 20%), Container E (7/40, 17.5%) and Container D (3/40, 7.5%).

Container handled most frequently by individual collaborators

When asked to answer about the container handled most frequently before among Containers A through E, Container A was answered by the largest number of collaborators (29/40, 72.5%), followed by Container C (8/40, 20%), Container E (2/40, 5.0%), Container D (1/40, 2.5%) and Container B (0/40, 0%).

Factors determining the ease of using liquid medication containers

When rated with NRS, the median score was highest at 7.8 with “1: Graduations on the container,” second highest at 7.2 with “5: Ease of cap opening/closing,” followed by 6.0 with “3: Presence/absence of inner stopper nozzle,” and 5.4 with “2: Shape of the container” and “4: Shape of the cap” (Figure 3). The score did not differ greatly between any two of “2: Shape of the container,” “3: Presence/absence of inner stopper nozzle”, and “4: Shape of the cap.”

Figure 3 Factors determining the ease of using liquid medication containers (n=40, Steel-Dwass test **P<0.001, * P<0.01).

CR caps

Recognition of CR caps

To the question “Do you know what a CR cap is?” (n=40), 22.5% (9/40) answered “Yes, I do.” The answer to this question was “Yes” by 7 of the 30 collaborators aged 40-49 (these 7 collaborators accounting for 18.0% of the entire study population) and 2 of the 5 collaborators aged 30-39 (accounting for 5.0%). All collaborators at age 20-29 (1 collaborator) and 50-59 (4 collaborators) answered “I don’t know.” Thus, the extent of knowledge about the CR cap was low.

After the CR cap was presented, each collaborator was asked “Have you used any CR cap before?” (n=40). To this question, 30.0% (12 collaborators) answered “I have used it.” The answer to this question was “Yes” by 9 of the 30 collaborators aged 40-49 (these 9 collaborators accounting for 22.5% of the entire study population) and 3 of the 5 collaborators aged 30-39 (accounting for 7.5%). All collaborators at age 20-29 (1 collaborator) and 50-59 (4 collaborators) answered “I have never used it.”

Time taken to open the CR cap

Without given any particular explanation in advance, individual collaborators were asked to open the CR cap, and the time taken for opening was measured. Of the 40 collab-orators, 29 were able to open the cap in 30 seconds and 11 were unable to open it in 30 seconds. The median time taken for opening the cap was 8 seconds (IQR: 6.5-15) among the 29 collaborators who were able to open the cap in 30 seconds. Between the group having successfully opened the cap in 30 seconds and the group having failed to do so, there was no significant difference in the pinching power, but there was a significant difference in age (Wilcoxon rank sum test, p=0.0494).

The 11 collaborators having failed to open the cap in 30 seconds were asked to open the cap again after a leaflet was presented to them. In the second attempt, 10 out of these 11 collaborators were able to open the cap in 30 seconds. The median time taken for opening the cap was 8 seconds (IQR: 6.75-11.25). One collaborator (age 40-49, pinching power 10.0 kg) took 58 seconds to open the cap.

About CR caps

To the question “Do you want to use the CR cap from now on?” (n=40), 55.0% (22 collaborators) answered “Yes, I want to use it” and 42.5% (17 collaborators) answered “No, I don’t want to use it.” The remaining 2.5% (1 collaborator) gave no answer. The answer to this question was “Yes” by 17 of the 30 collaborators aged 40-49 (these 17 collaborators accounting for 42.5% of the entire study population), 3 of the 5 collaborators aged 30-39 (accounting for 7.5%), 2 of the 4 collaborators aged 50-59 (accounting for 5.0%) and none of the 1 collaborator aged 20-29 (accounting for 0.0%).

Table 7 shows the free comments given to the CR cap.

Regarding the containers used for dispensing oral-dose liquid medication in Japan, the present study was undertaken to evaluate the time taken for measuring the liquid from containers and the ease of using the containers, with the goals of exploring a desirable form of this kind of container and investigating the degree of recognition about the CR cap among general users and the ease/problems of opening the cap by such users.

According to a survey conducted at a national pediatric hospital in Japan about intake of oral-dose pediatric medication, powder was the most frequently used form of medication for patients less than age 6 years, and liquid (including syrup and suspension) was the second most frequent form of medication prescribed for such patients.⁷ If a similar survey were conducted at general hospitals or clinics across the country, different results may be obtained. In Japan, for management of fever due to infections (cold, influenza) in pre-school age children, acetaminophen syrup is frequently prescribed, accompanied by other agents for symptomatic therapy such as carbocysteine syrup and tipepidine hibenzate syrup.

The present survey used simple syrup as a phantom drug solution, assuming the use of syrup preparations in clinical practice. The time taken by the collaborators for measuring this test liquid was shortest from Container A and second shortest from Container B. Containers A and B were designed to enable directly measuring the liquid from the container into the cup without using a spuit, thus simplifying the measuring procedure and shortening the time taken. Spilling of the liquid occurred only from Container C and D. As suggested in the free comments given by collaborators, liquid spilling from these two containers was probably attributable to dripping from the spuit, and the spuit’s design (the ball is hard and does not resume its original form soon after compression). The trouble of measuring an excess volume of the liquid and returning the excess liquid into the container occurred much more frequently with Container C and D. This seems to be attributable to dripping of the liquid during aspiration with a spuit from the container. The spuit used for Container C and D was of a simple design for which high accuracy in measuring could not be expected. This kind of spuit was shown in this survey to be unsatisfactory in terms of basic functions (tending to cause dripping, and slow in resumption of the original form after compression due to the hard ball). As a result, accurate measuring in short time was difficult with this kind of spuit.

In evaluation by NRS of usability of liquid medication containers, the “ease of measuring the liquid” was higher with Containers B, C and D than with Container A. The “ease of cap opening/closing” did not differ significantly between any two of the containers. The “hygienic design” score was high with Containers D and B. In the present survey, evaluation was not affected by the graduations marked on individual containers because the test was conducted under the same setting of graduations for all of Containers A through D. The shape of cap was the same for all containers except for Container B.

The time taken for measuring the liquid from each container did not correlate with age or pinching power of the collaborators. In analysis of the correlation of age and pinching power with the other parameters of container usability, the only correlation observed was a weak negative correlation between age and “ease of cap opening/closing” of Container D. The cap for Container D was the same as the cap for Containers A and C, but it has a built-in spuit at the center of the cap. As a result, the cap-opening procedure for Container D differs from that for Containers A and C. This difference and the lack of past experience of using this type of container may be associated with the finding obtained about Container D mentioned above.

When asked about “the most easily usable container (comprehensive evaluation),” the score was highest with Container B, followed by Container D. This result is not fully consistent with the findings about the median time taken for measuring and the other parameters of usability (ease of measuring the liquid, ease of cap opening/closing, hygienic design). Container B has a small diameter nozzle, while Container D has a spuit integrated with the container. Free comments given by the collaborators who selected Container B as the most easily usable container included “easy to make fine adjustments,” “spilling unlikely,” “simple nozzle design allowing easier measuring” and “large cap easy to grip.” Free comments about Container D included “possible to store the spuit together with the container,” “hygienic design” and “dripping less likely than Container C.” These comments indicate that the collaborators attached importance to hygienic, accurate and careful measurement, i.e., to the features such as the availability of an auxiliary device (small diameter nozzle or integrated spuit) attached to the container for accurate liquid measurement, the ease of making minor adjustments for accurate liquid measurement, and the spuit’s basic function associated with prevention of dripping. On the other hand, Container A was probably appraised low because of unavailability of an auxiliary device attached to the container for accurate liquid measuring. Collaborators found problems with Container A because the opening of this container is too wide to enable easy minor adjustments at the time of measuring the liquid although this container allows the most rapid measurement. Container B was found to have a problem in that the spuit used for this container was difficult to store in a hygienic manner. With Containers A and B, the liquid is placed into the cup directly from the container. Thus, the container is first put upside down to pour some volume of the liquid into the cup. The container is then put upright, and the volume in the cup is checked by reading the decrease in volume level on the graduations. By repeating this sequence of steps, the volume for a single dose (equivalent to one scale of graduations marked on the container) is measured. With Containers C and D, on the other hand, the container is kept upright and a spuit is placed into the container to measure the liquid. A free comment given by the collaborator who selected Container B says that it is desirable if Container B has graduations possible to read when the container is put upside side. When asked about the past experience of use, Container A had been used by the largest number of collaborators before (39 out of the 40 collaborators). The frequency of past use was also highest with Container A (29 collaborators). However, the containers used frequently were not necessarily the containers easy to use.

To the question “Which of Container A or E is more desirable in terms of graduations?”, an overwhelming majority of the collaborators answered the print type graduations to be easier to read. To the question “Which of Container C or D is more desirable in terms of spuit design?”, 60% of the collaborators selected Container D and 37.5% selected Container C. Regarding Container D, there was a comment that this container integrated with the spuit is hygienic and is easy to store. Regarding Container C, on the other hand, there was a comment that the spuit attached to this container can reach the bottom, thus allowing easy measuring without being affected by the volume of liquid contained. However, as mentioned above, the troubles of liquid spilling or the need of returning the excess measured liquid into the container occurred mostly with Containers C and D, and there were many comments pointing out the likelihood of dripping from the spuit tip or inability of aspirating the liquid from the container bottom. These comments seem to reflect the demand to a spuit design which is less likely to cause dripping and allows the tip to reach the bottom of the container.

In analysis of factors making the liquid medication containers easy to use, the NRS score was highest with “graduations on the container” (median: 8) and second highest with “ease of cap opening/closing.” After these factors, “shape of the container,” “presence/absence of inner stopper nozzle” and “shape of the cap” had similar scores (median: 5 each). These results suggest that greater importance was attached by the collaborators to the design of graduations needed for accurate measurement of the liquid to be administered, rather than to the functionality of the container itself.

Taken together, users in general are demanding liquid medication containers with printed graduations enabling more accurate measurement, being hygienic and easy to store.

According to the “Report on Monitoring of Hospitals about Health Hazards Related to Household Products in 2018” by the Ministry of Health, Labour and Welfare (MHLW),¹¹ the reports on erroneous oral intake by children (total 626 cases) most frequently pertained to cigarette (20.8%), followed by drugs/quasi drugs (17.4%). MHLW has informed medial facilities and pharmacies about the need of ensuring measures for prevention of erroneous intake of drugs by children,^12,13 accompanied by disseminating the relevant precautions to guardians by local communities and issuance of a proposal for promotion of CR container use.¹³ At present, however, CR packages for pharmaceutical products have not been actively introduced in Japan. Also at insurance-covered medical facilities and pharmacies, CR packages/containers have not yet been actively used when providing the dispensed drugs in multi-divided portions in the forms of tablet, powder or liquid. The Japanese Pharmacopeia also has no provision about the testing method. concerning CR packages. To take an example of prescription drugs in the form of tablets, the press-through-pack (PTP) packages are now being used most frequently, and the form of bottle is very rare. There is no standard about PTP in the Japanese Pharmacopeia and this also serve as a hurdle against extensive adoption of CR packages/containers. Also for household products, CR packages/containers have been adopted only in limited products (e.g., disposable lighters) and have not yet been used for cleansers and other products used during daily living, except for a limited range of products such as imported products. Thus, from the viewpoint of consumers in Japan, there are few chances for them to handle CR packages/containers in their daily life.

To the question “Do you know what the CR cap is?”, only 22.5% (9 collaborators) answered they knew about it. This result suggests that the term “CR (Child Resistance)” has not spread widely. When no explanation was given in advance, opening the CR cap in 30 seconds was possible in 11 collaborators. The pinching power did not differ significantly between the group having successfully opened the CR cap and the group having failed to do so. However, age differed significantly between these two groups, suggesting that the older collaborators were less familiar with the CR cap. The results additionally suggest that the action of opening the cap by rotating while pushing has not become familiar in their daily life.

To the question “Do you want to use the CR cap from now on?”, 55.0% of the collaborators answered “Yes, I want to use it” and 42.5% answered “No, I don’t want to use it.” Many of the collaborators having answered “Yes, I want to use it” gave a comment that this cap is safe because it can prevent erroneous intake, while the collaborators having answered “No, I don’t want to use it” gave comments such as “difficult to open it even after reading the leaflet,” “sometimes cannot be opened depending on the state of closure or the way of force application” and “making me irritated when busy.” There was also a comment indicating the necessity of modifying the current design so that it can be opened easily even by elderly people or individuals with low physical power. What is functionally required to open the push-and-rotate type CR cap includes the pushing power and the rotating power. It seems necessary to review the current CR cap design, taking into account the physical characteristics of Japanese people.

The results of the present study indicate that the collaborators to this study attached importance to the accuracy in measuring the liquid, the ease of reading the graduations and the design allowing hygienic handling as the factors determining the most easily usable liquid medication containers. The results additionally show that the recognition of the CR cap among people is not high at present. Pharmacists and other healthcare professionals in Japan should pay attention to these findings and endeavor to facilitate extensive adoption of containers designed to enable accurate measurement of the liquid and to prevent erroneous drug intake by children from the viewpoint of safety management. Discussions are needed also about how to resolve the increased burdens on healthcare providers such as increase in the container-related expenses at medical facilities/pharmacies, and increase in the time needed for medication-related guidance such as guidance about how to use the container. At present, education for appropriate use of drugs and prevention of drug abuse is provided within the framework of compulsory education programs. In addition to these programs, educational campaigns are needed from now on also for prevention of erroneous intake of drugs and household products by infants and young children. In Japan, the tendency for population ageing and low birth rate has been increasing, with the percentage of elderly population to reach 35.3% in 2040 according to an estimate.¹⁴ Now, active discussions are needed about packages and containers functioning as CRSF (Child Resistant & Senior Friendly) Packaging.

The authors would like to express their gratitude to all collaborators who participated in the survey. This work was supported by JSPS KAKENHI Grant Number JP21K02339.

The authors declare no conflicts of interest.

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