Kato Ginjiro, Mitome Hidemichi, Takeda Syu, Hidaka Noriaki, Tanaka Mamoru, Akira Kazuki
Laboratory of Pharmaceutical Analytical Chemistry, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime, 790-8578, Japan.
Division of Pharmacy, Ehime University Hospital, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan.
J Pharm Health Care Sci. 2024 Nov 18;10(1):73. doi: 10.1186/s40780-024-00396-0.
A simple suspension method, where solid formulations are disintegrated and suspended by being soaked in warm water followed by tube administration, is widely used, especially for elderly patients with dysphagia in Japanese clinical settings. However, there is insufficient information on drug stability in the simple co-suspension of multiple formulations especially including acidic or alkaline ones. The influence of occasional prolonged soakage on drug stability is also of concern. In this study, the chemical stability of typical β-lactam antibiotics, amoxicillin, and cefcapene pivoxil hydrochloride, was investigated in simple co-suspensions with magnesium oxide (MgO), which is frequently used as an alkaline laxative for the elderly.
Amoxicillin (capsule) or cefcapene pivoxil hydrochloride (tablet) was placed with or without MgO (tablet) in a centrifuge tube containing warm water (55 °C). The tube was allowed to stand for 10 min or 5 h at room temperature and simple suspensions were prepared. The suspensions were then treated with large amounts of solvents and neutralized using a weakly acidic cation exchange resin. The resulting solutions were analyzed by high-performance liquid chromatography. The degradation products were identified by mass spectrometry and nuclear magnetic resonance spectroscopy.
Amoxicillin was found to be partially degraded to amoxicilloic acid and amoxicillin diketopiperazine by the co-suspension with MgO. The degree of degradation increased with the prolonged soaking. The recovery rates of cefcapene pivoxil decreased due to the poor solubility in the co-suspensions with MgO and no degradation product of the drug was observed.
Amoxicillin and MgO should be independently suspended because of the chemical instability of amoxicillin. This study has also indicated there is a degradation risk after prolonged soaking. It should be noted that the poor water solubility of cefcapene pivoxil under alkaline conditions may affect the absorption process as well as tube passability.
一种简单的混悬方法被广泛应用，即固体剂型通过浸泡在温水中崩解并混悬，随后通过管道给药，在日本临床环境中尤其适用于吞咽困难的老年患者。然而，关于多种剂型尤其是含酸性或碱性剂型的简单混合混悬液中药物稳定性的信息不足。偶尔的长时间浸泡对药物稳定性的影响也令人担忧。在本研究中，研究了典型的β-内酰胺类抗生素阿莫西林和盐酸头孢卡品酯在与氧化镁（MgO）的简单混合混悬液中的化学稳定性，氧化镁常用于老年患者的碱性泻药。
将阿莫西林（胶囊）或盐酸头孢卡品酯（片剂）与或不与MgO（片剂）置于含有温水（55°C）的离心管中。将试管在室温下静置10分钟或5小时，制备简单混悬液。然后用大量溶剂处理混悬液，并用弱酸性阳离子交换树脂中和。所得溶液通过高效液相色谱分析。通过质谱和核磁共振光谱鉴定降解产物。
发现阿莫西林与MgO混合混悬后部分降解为阿莫西林酸和阿莫西林二酮哌嗪。降解程度随浸泡时间延长而增加。由于在与MgO的混合混悬液中溶解度差，盐酸头孢卡品酯的回收率降低，且未观察到该药物的降解产物。
由于阿莫西林的化学不稳定性，阿莫西林和MgO应分别混悬。本研究还表明长时间浸泡后存在降解风险。应注意的是，盐酸头孢卡品酯在碱性条件下的水溶性差可能会影响吸收过程以及管道通过性。
