Purpose: Among the various types of drug formulations available, such as tablets, capsules, and granules, tablets are the most widely used because of ease of handling, as well as convenience for carrying and storage. However, many patients have noted difficulties with swallowing tablets with a large diameter. Mini-tablets with a diameter ≤4 mm have been widely studied and developed, and are considered to be easier to swallow as compared to conventional tablets, which usually have a diameter >4 mm. Decreased tablet diameter may improve patient adherence to medication and reduce the risk of aspiration of tablets. On the other hand, as tablet diameter is reduced, patients have more difficulties with picking them up and handling, especially elderly with functional problems with their fingers or poor eyesight. Thus, in regard to tablet diameter, ease of swallowing is countered by more difficulties with handling, both of which can have effects on prescription adherence. Few studies have examined the relationship of tablet diameter with swallowing and handling using various sized mini-tablets. For the present clinical trials, we produced tablets ranging in size from 2‒8 mm, and evaluated them for ease of swallowing and handling.
Methods: We manufactured tablets with 7 different sizes (2, 3, 4, 5, 6, 7, 8 mm). All volunteers provided written informed consent to participate in this study, which was conducted in accordance with the Declaration of Helsinki and subsequent amendments. The study protocol was approved by the Ethics Committee of the University of Shizuoka. To evaluate ease of swallowing (swallowing trial), 17 healthy young volunteers (14 males, 3 females; age 23.1±1.2 years, mean ± standard deviation) participated in a randomized crossover trial. Each volunteer freely filled a cup with water from a 500-mL bottle and then was asked to use the minimum volume of water required to smoothly consume each tablet. The amount of water was measured based on the weight of the cup and bottle. After taking the tablet with drinking water, they were asked to evaluate ease of swallowing using a visual analogue scale (VAS), with the most difficult sensation for swallowing marked at 100 mm, as well as a 5-point scale, with the most difficult sensation for swallowing marked at 5 and the easiest sensation for swallowing at 1. In another randomized crossover trial conducted to examined ease of handling (handling trial), 25 elderly patients (14 males, 11 females; age 80.4 ± 6.9 years) participated. Each patient was asked to pick up 10 tablets from a dish and place them in a medication cup 30 cm distant from the dish, one by one. We determined total time required to transfer all of the tablets to the medication cup. After finishing, they were asked to evaluate the ease of handling the tablets using a VAS, with the most difficult sensation for handling marked at 100 mm.
Results: For the swallowing trial, the amount of water required to swallow tablets sized 2 and 8 mm in diameter was 31.4 and 13.0 mL, respectively (Fig. 1A). We noted that less water was needed for swallowing tablets as the diameter was reduced. VAS scores for ease of swallowing were also decreased for tablets 5 mm as compared to those 8 mm in diameter (Fig. 1B). For tablets <4 mm in diameter, VAS scores were nearly the same. The 5-point scale results were similar to those with the VAS, as most of the volunteers answered “easier to swallow” for tablets sized <5 mm. As for the handling trial, the time required for the elderly patients to transfer all tablets was reduced from 32.8 to 22.2 seconds when the diameter of the tablets was from 2 to 4 mm (Fig. 2A). With tablets >5 mm, the time for handling was nearly the same regardless of size. VAS results for handling tablets was similar to the evaluation of handling time (Fig. 2B). Our findings suggested that tablets >5 mm are easier to handle by elderly individuals.
Conclusion: The present results indicate that tablets <5 mm in diameter are easy to swallow, while those >5 mm offer good handling. Thus, a 5-mm tablet seems to adequately fulfill needs in regard to both swallowing and handling. We concluded that a range of tablet diameters is needed to meet the requirements of swallowing and handling, while a diameter of 5 mm may be the most appropriate for ease of both actions.
Shinya Uchida– Associate professor, University of Shizuoka, Shizuoka
Homare Kurashima– University of Shizuoka, Shizuoka
Yuka Ishizaka– University of Shizuoka, Shizuoka
Shimako Tanaka– Assistant professor, University of Shizuoka, Shizuoka
Yasuharu Kashiwagura– Assistant professor, University of Shizuoka, Shizuoka
Yuzuru Ito– University of Shizuoka, Shizuoka
Noriyuki Namiki– Professor, University of Shizuoka, Shizuoka