用PCCA悬浮液载体配制儿童口服悬浮液治疗心血管疾病的稳定性研究。

Q4 Medicine
Courtaney Davis, Kendice Ip, Daniel Banov, Oleksandr Zdoryk
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引用次数: 0

摘要

儿科心脏病学的制药领域涉及到几个关键活性药物成分(api)的使用,这些成分经过精心挑选,以解决遇到的各种情况。氢氯噻嗪、卡托普利和美托洛尔是该清单的一部分,其选择基于严格的标准,包括已证实的疗效、良好的安全性和儿童使用的适用性。这些有效成分属于不同的药理学组——一种是血管紧张素转换酶抑制剂(卡托普利),一种是噻嗪类利尿剂(氢氯噻嗪),一种是-受体阻滞剂(美托洛尔)——用于治疗各种心血管疾病。这些药物的商业药物形式无法为儿科患者提供,在剂量选择方面留下了空白。因此,为这一人群服务的主要手段是通过使用纯粉状药物或商业片剂临时配制混悬液。本研究的目的是研究三种不同的复合儿科口服心血管混悬液的物理化学和微生物稳定性,这三种混悬液分别含有卡托普利、氢氯噻嗪和酒石酸美托洛尔,并使用PCCA悬浮液配制。研究设计包括两种原料药浓度,以在一个浓度范围内提供稳定性研究:卡托普利(1mg /mL和5mg /mL)、氢氯噻嗪(5mg /mL和10mg /mL)和美托洛尔(1mg /mL和10mg /mL)。建立了超高效液相色谱(UHPLC)法测定悬浮液中卡托普利、氢氯噻嗪和美托洛尔的化学稳定性。氢氯噻嗪和美托洛尔混悬液样品分别保存在温度为25±2℃,相对湿度为60±5%的琥珀色塑料处方瓶中,卡托普利混悬液保存在5±3℃。在以下时间点对样本进行分析:0、7、14、30、60、90和180天。采用了各种强制降解条件,包括酸性、碱性、氧化和热降解。结果表明,潜在的干扰降解物不影响原料药的分析峰,并确定了导致该悬浮液中原料药显著降解的因素。物理性质,如pH值和外观也进行了观察。所有测量都是重复进行的。在贮藏过程中进行抑菌效果试验以控制微生物的生长。目前的研究表明,悬浮心血管混悬液在180天内,卡托普利(在冰箱中储存时)和氢氯噻嗪和酒石酸美托洛尔(在室温下储存时)在物理、化学和微生物方面都是稳定的,保留不少于90%的标记药物浓度。本研究为氢氯噻嗪、酒石酸美托洛尔和卡托普利的液体剂型提供了一种可行的复合替代品,具有足够的过期日期,以满足患者的需要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Stability Study of Pediatric Oral Suspensions Formulated with PCCA SuspendIt Vehicle Used for the Treatment of Cardiovascular Disease.

The pharmaceutical landscape in pediatric cardiology involves the use of several key active pharmaceutical ingredients (APIs) that have been carefully selected to address the diverse range of conditions encountered. Hydrochlorothiazide, captopril and metoprolol are part of this list, selected based on stringent criteria that included proven efficacy, a favorable safety profile, and suitability for pediatric use. These active ingredients belong to different pharmacological groups - an angiotensin-converting enzyme inhibitor (captopril), a thiazide diuretic (hydrochlorothiazide) and a beta-blocker (metoprolol) - and are used to treat a variety of cardiovascular problems. Commercial pharmaceutical forms of these drugs are not available for pediatric patients, leaving a gap in dosing options. Therefore, the primary means of serving this population is through extemporaneous compounding of suspensions using pure drug powder or commercial tablets. The objective of this study was to investigate the physicochemical and microbiological stability of three distinct compounded pediatric oral cardiovascular suspensions, that contain captopril, hydrochlorothiazide, and metoprolol tartrate, and are formulated using PCCA SuspendIt. The study design included two concentrations of each API to provide stability investigation over a bracketed concentration range: captopril (1 mg/mL and 5 mg/mL), hydrochlorothiazide (5 mg/mL and 10 mg/mL), and metoprolol (1 mg/mL and 10 mg/mL). Ultra-high-performance liquid chromatography (UHPLC) methods were developed and validated for the determination of the chemical stability of captopril, hydrochlorothiazide, and metoprolol in SuspendIt. Samples of hydrochlorothiazide and metoprolol suspensions were stored in plastic amber prescription bottles at the temperature 25±2 °C, relative humidity 60±5 %, and captopril suspensions at 5±3 °C. Samples were analyzed at the following time points: 0, 7, 14, 30, 60, 90, and 180 days. Various forced degradation conditions were employed, including acidic, basic, oxidative, and heat degradation. The results revealed that potential interfering degradants do not affect the analytical peaks of the drug substance, and the factors contributing to the significant degradation of the drug substance in the suspension were identified. Physical properties such as pH and appearance were also observed. All measurements were performed in duplicate. Antimicrobial efficacy tests were performed to control microbial growth during storage. The current study demonstrates that SuspendIt cardiovascular suspensions are physically, chemically and microbiologically stable for 180 days for captopril (when stored in the refrigerator) and hydrochlorothiazide and metoprolol tartrate (when stored at room temperature), retaining not less than 90% of the labeled drug concentrations. This study provides a viable compounded alternative for hydrochlorothiazide, metoprolol tartrate and captopril in a liquid dosage form with an adequate beyond-use-date to meet patient needs.

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来源期刊
CiteScore
0.40
自引率
0.00%
发文量
62
期刊介绍: The International Journal of Pharmaceutical Compounding (IJPC) is a bi-monthly, scientific and professional journal emphasizing quality pharmaceutical compounding. IJPC is the only publication that covers pharmaceutical compounding topics relevant and necessary to empower pharmacists to meet the needs of today"s patients. No other publication features hands-on, how-to compounding techniques or the information that contemporary pharmacists need to provide individualized care.
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