Saito Jumpei, Yamatani Akimasa, Kojima Yuna, Nakakuni Masayoshi, Nakano Kosuke, Hirose Kaoru, Nakamura Hidefumi, Hanawa Takehisa, Akabane Miki
Department of Pharmacy, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan.
Pediatric and Perinatal Medicine, Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose-shi, Tokyo 204-0004, Japan.
Pharmaceutics. 2025 Apr 19;17(4):535. doi: 10.3390/pharmaceutics17040535.
Compounding is performed to adjust dosages and support medication for children. In Japan, tablets are crushed, diluted with lactose, and stored in bottles or sachets until use, but the stability and impact on dissolution of the ingredients after crushing have not been evaluated. Using a database established by the National Center for Child Health and Development in collaboration with 11 medical facilities, the status of tablet crushing was investigated. Commonly compounded drugs were selected as the target drugs. The selected drugs were sieved through a 500 μm mesh after crushing and diluted with lactose hydrate. The stability at 25 ± 2 °C/60 ± 5% relative humidity and the dissolution of the ingredients were evaluated after storing them for up to 120 days under the following conditions: (I) stored in a closed polycarbonate bottle (closed), (II) bottle opened once a day (in-use), or (III) stored in a laminated cellophane and polyethylene sachet (laminated). The changes in the ingredient content and dissolution behavior were evaluated in accordance with the Japanese Pharmacopoeia. Five cardiovascular drugs (amlodipine besylate, carvedilol, propranolol hydrochloride, hydrochlorothiazide, and tadalafil) were selected as target drugs. No more than 10% change in ingredient content was observed for all five formulations compared to day 0. In addition, no related substances (impurities) were detected at more than 0.01%. There was no change in the dissolution rate of the samples after 120 days of storage under each storage condition. The five cardiovascular drugs commonly compounded for children in Japan maintained their pharmaceutical quality after compounding, even after long-term storage.
进行复方制剂调配是为了调整剂量并为儿童提供药物支持。在日本，片剂被碾碎，用乳糖稀释，然后储存在瓶子或药袋中备用，但碾碎后成分的稳定性及其对溶出度的影响尚未得到评估。利用国立儿童健康与发展中心与11家医疗机构合作建立的数据库，对片剂碾碎的情况进行了调查。选择常用的复方制剂药物作为目标药物。将碾碎后的选定药物通过500μm筛网筛分，并用乳糖水合物稀释。在25±2℃/相对湿度60±5%的条件下储存长达120天后，在以下条件下评估其稳定性和成分的溶出度：(I)储存在密闭的聚碳酸酯瓶中（密闭），(II)每天打开一次瓶子（使用中），或(III)储存在层压玻璃纸和聚乙烯药袋中（层压）。根据日本药典评估成分含量和溶出行为的变化。选择了五种心血管药物（苯磺酸氨氯地平、卡维地洛、盐酸普萘洛尔、氢氯噻嗪和他达拉非）作为目标药物。与第0天相比，所有五种制剂的成分含量变化均不超过10%。此外，未检测到相关物质（杂质）含量超过0.01%。在每种储存条件下储存120天后，样品的溶出率没有变化。日本常用的五种儿童复方心血管药物在调配后，即使长期储存，仍能保持其药品质量。
