Division of Clinical Pharmacology, Department of Pediatrics, School of Medicine, University of Utah, Salt Lake City, Utah, United States of America.
Department of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, University of Utah, Salt Lake City, Utah, United States of America.
PLoS One. 2020 Jul 10;15(7):e0232435. doi: 10.1371/journal.pone.0232435. eCollection 2020.
Anxiety disorders (AD) are the most common mental conditions affecting an estimated 40 million adults in the United States. Amiloride, a diuretic agent, has shown efficacy in reducing anxious responses in preclinical models by inhibiting the acid-sensing ion channels (ASIC). By delivering amiloride via nasal route, rapid onset of action can be achieved due to direct "nose-to-brain" access. Therefore, this study reports the formulation, physical, chemical, and microbiological stability of an extemporaneously prepared amiloride 2 mg/mL nasal spray. The amiloride nasal spray was prepared by adding 100 mg of amiloride hydrochloride to 50 mL of sterile water for injection in a sterile reagent bottle. A stability-indicating high-performance liquid chromatography (HPLC) method was developed and validated. Forced-degradation studies were performed to confirm the ability of the HPLC method to identify the degradation products from amiloride distinctively. The physical stability of the amiloride nasal spray was assessed by pH, clarity, and viscosity assessments. For chemical stability studies, samples of nasal sprays stored at room temperature were collected at time-points 0, 3 hr., 24 hr., and 7 days and were assayed in triplicate using the stability-indicating HPLC method. Microbiological stability of the nasal spray solution was evaluated for up to 7 days based on the sterility test outlined in United States Pharmacopoeia (USP) chapter 71. The stability-indicating HPLC method identified the degradation products of amiloride without interference from amiloride. All tested solutions retained over 90% of the initial amiloride concentration for the 7-day study period. There were no changes in color, pH, and viscosity in any sample. The nasal spray solutions were sterile for up to 7 days in all samples tested. An extemporaneously prepared nasal spray solution of amiloride hydrochloride (2 mg/mL) was physically, chemically, and microbiologically stable for 7 days when stored at room temperature.
焦虑症 (AD) 是最常见的精神疾病，据估计，美国有 4000 万成年人受其影响。利尿剂阿米洛利通过抑制酸感应离子通道 (ASIC)，在临床前模型中显示出减少焦虑反应的功效。通过鼻内途径给予阿米洛利，可以通过直接“鼻脑”通路实现快速起效。因此，本研究报告了一种临时制备的 2mg/mL 阿米洛利鼻喷雾剂的制剂、物理、化学和微生物稳定性。阿米洛利鼻喷雾剂通过在无菌试剂瓶中将 100mg 盐酸阿米洛利加入 50mL 无菌注射用水中制备。建立并验证了一种稳定性指示高效液相色谱 (HPLC) 方法。进行强制降解研究以确认 HPLC 方法能够独特地识别阿米洛利的降解产物。通过 pH 值、澄清度和粘度评估来评估阿米洛利鼻喷雾剂的物理稳定性。对于化学稳定性研究，在室温下储存的鼻喷雾剂样品在 0、3 小时、24 小时和 7 天时收集，并使用稳定性指示 HPLC 方法一式三份进行测定。根据美国药典 (USP) 第 71 章概述的无菌试验，评估鼻喷雾剂溶液的微生物稳定性，最长可达 7 天。稳定性指示 HPLC 方法可识别阿米洛利的降解产物，而不受阿米洛利的干扰。在 7 天的研究期间，所有测试溶液均保留初始阿米洛利浓度的 90%以上。任何样品均未发生颜色、pH 值和粘度变化。在所有测试的样品中，鼻喷雾剂溶液在 7 天内均保持无菌。当在室温下储存时，盐酸阿米洛利（2mg/mL）的临时制备的鼻喷雾剂溶液在 7 天内保持物理、化学和微生物稳定性。
