Experimental Study on Patient Preferences Regarding the Shape and Size of Medical Tablets and Capsules Using Three-Dimensionally Printed Plastic Model Formulations.

BACKGROUND: Tablets and capsules are the most common dosage forms. However, ease of use and/or swallowing influences patients' compliance. OBJECTIVE: To identify patients' preferences regarding the three-dimensional size of medical tablets/capsules. METHODS: Eighteen cylindrical-, oblong-, and oval-shaped model formulations having different sizes were prepared by three-dimensional printing using polylactic acid. Participants (40 patients visiting a pharmacy in Japan) evaluated the difficulty of picking up and swallowing these model formulations by touching/observing them, and completed a questionnaire. The visual analogue scale (VAS) was used to evaluate each sample, and the relationship of VAS scores to the major axis, thickness, I2 (the sum of major/minor axes) and I3 (the sum of major/minor axes and thickness) of the model formulations was evaluated by ANOVA followed by Tukey's test. RESULTS: Female participants showed lower VAS scores (less difficult) for picking difficulty compared with male participants, and those taking many drugs showed higher VAS scores (more difficult) for swallowing difficulty compared with those taking fewer drugs. Otherwise, age, gender, disease status, number of drugs usually taken, and ingestion problems did not greatly influence the evaluation. Overall, larger model formulations showed less picking difficulty, but greater swallowing difficulty. Model formulations 2 mm thick or less were harder to pick up, whereas those 6 mm thick or more were harder to swallow. I3 values greater than 20-22 mm were associated with a negative evaluation by participants. CONCLUSION: Participants in this study preferred model formulations with an I3 value below 22 mm and a thickness of 2-6 mm.

Threshold Size of Medical Tablets and Capsules: Based on Information Collected by Japanese Medical Wholesaler.

BACKGROUND: Medical tablets and capsules are superior with regard to portability and are the most common dosage form in Japan. However, their large size often results in difficulties during ingestion, sometimes leading to reduced medication adherence. OBJECTIVE: The authors used postmarketing surveillance data to determine the threshold size of medical tablets and capsules that patients feel are too large to ingest. PATIENTS AND METHODS: The marketing specialists of Toho Pharmaceutical Co., Ltd. collected opinions of patients and medical workers (November 2014-April 2016). Regarding 709 reports from patients stating that the tablet or capsule for too large for ingestion, a dataset was prepared from package inserts of the reported drugs. Two analyses were conducted: histogram analysis of size distribution and geometric analysis using linear approximation. Six indices of tablet/capsule size were considered: length; length + width; length + width + depth; length × width; length × width × depth; and weight. RESULTS: Histogram analysis revealed that length + width + depth is an excellent index of tablet/capsule size, and negative reports on tablet/capsule size drastically increase when this index is ≥21 mm. Geometric analysis using linear approximation also revealed similar results. CONCLUSION: The threshold size of tablets/capsules that patients feel are too large to ingest is length + width + depth = 21 mm. Therefore, when designing or altering tablets/capsules, if length + width + depth is ≥21 mm, the drug should be scored, split into smaller doses, or redesigned as an orally disintegrating formulation.

Characteristics of "Hard-to-Use" Press-Through-Package Sheets: An Analysis of Information Collected by Marketing Specialists of a Japanese Medical Wholesaler.

BACKGROUND: Press-through-package (PTP) sheets are common forms of packaging for medicines in Japan. However, patients and/or pharmacists have reported difficulty in extracting tablets or capsules from some PTP sheets. OBJECTIVE: We used postmarketing surveillance data to identify the characteristics of PTP sheets that patients and pharmacists feel are "hard to use". METHODS: Marketing specialists of Toho Pharmaceutical Co., Ltd. canvassed patients and medical workers during November 2014-April 2016. Among 1,129 anonymous reports of products being "hard to use", we identified 39 products with 5 or more reports (Problem group). We compared the sizes of the drugs and PTP pockets, the size ratio, the material used for the front of PTPs, the shape of the pockets, the thickness of the pocket wall, and the force needed to release the drug from the PTP (press-out force: POF) in this Problem group with those in a Control group of 97 problem-free products. RESULTS: Logistic regression analyses revealed that a bigger pocket, a smaller drug size and a smaller drug-pocket size ratio increase the risk of being "hard to use". Regarding the material, aluminum, PCTFE and PE increase the risk, while PP and PVC decrease the risk. Other factors had no significant influence. CONCLUSION: Pockets in PTP sheets should be designed so as to minimize the gap between the drug and the pocket, and PP or PVC should be used as the front material instead of aluminum, PCTFE or PE. Our results suggest that marketing specialists can play effective roles in postmarketing surveillance.

Elevated plasma resistin concentrations in patients with liver cirrhosis.

BACKGROUND: Resistin, an adipose-derived polypeptide hormone, has been proposed to be a candidate in insulin resistance, although its role in humans remains controversial. Liver cirrhosis (LC) is characterized by an elevated number of circulating proinflammatory cytokines, hyperinsulinemia and insulin resistance. The aim of this study was to determine the plasma resistin levels in patients with LC. METHODS: Resistin levels were determined in 79 patients with LC and in 31 healthy controls. Patients included 34 with Child-Pugh grade A, 30 with Child's B and 15 with Child's C LC. Fasting plasma glucose, fasting plasma insulin, adiponectin, the homeostatic model assessment insulin resistance (HOMA-IR) index, quantitative insulin sensitivity check index (QUICKI) and biochemical parameters were also determined. RESULTS: Plasma resistin levels were 7.61 +/- 6.70 ng/mL in the LC patients and 3.38 +/- 1.68 ng/mL in the controls, respectively. The plasma resistin levels were significantly elevated in patients with LC in comparison to the controls (P < 0.01). The plasma resistin levels increased in a stepwise fashion in line with a higher grade according to Child-Pugh classification. Fasting plasma insulin, adiponectin and HOMA-IR index were also significantly elevated in patients with LC in comparison to controls. Inversely, QUICKI significantly decreased in patients with LC. According to Spearman's rank correlation, log resistin showed significantly positive correlation with fasting plasma insulin, log adiponectin, HOMA-IR index, and a negative correlation with QUICKI (P < 0.01). The plasma resistin levels did not correlate with sex, body mass index and fasting plasma glucose levels. CONCLUSION: The plasma resistin levels increased in patients with LC, thus showing a positive correlation with fasting plasma insulin, adiponectin, HOMA-IR index, and a negative correlation with QUICKI. Although a decreased extraction of resistin due to reduced liver function cannot be ruled out, resistin may contribute to insulin resistance in patients with LC. The pathophysiological roles of resistin in LC still require further investigation.

[A retrospective study of irinotecan plus fluorouracil and l-leucovorin chemotherapy for advanced and metastatic colorectal cancer].

We have treated 14 advanced and metastatic colorectal cancers with irinotecan (CPT-11) plus fluorouracil (5-FU) and l-leucovorin (l-LV) combination chemotherapy. The 14 patients consisted of 8 males and 6 females with a mean age of 65 years. We diagnosed adenocarcinoma of the colon in 10 patients and of the rectum in 4 patients. Four patients had liver metastases, five had lung metastases, and one had both, while one had lung and lymph node metastases, two had lymph node metastases and one had a local recurrence. The chemotherapy consisted of CPT-11 100 mg/m(2) div, as a 150-minute infusion, simultaneously l-LV 10 mg/m(2) div, as a 30-minute infusion, followed by 5-FU 500 mg/m(2) iv, as a bolus injection. This treatment was administered weekly for 2 weeks followed by a 2-week rest period and repeated every 4 weeks. All patients received this regimen as first-line chemotherapy. All patients were evaluated for efficacy 1 CR, 2 PR, 9 SD, and 2 PD. The overall response rate was 21.4% with a median time to progression of 8.1 months and a median survival time of 18.6 months. Grade 3 nausea, diarrhea and the suppression of white blood cells were seen in 3 patients, respectively. All other adverse reactions were mild (grade 1 or 2). Except for one patient,residual patients were able to receive the systemic chemotherapy on schedule. CPT-11/5-FU/l-LV combination chemotherapy appears to be effective first-line chemotherapy for advanced and metastatic colorectal cancer.