Stability of flucytosine 100 mg/mL suspension as an alternative to intravenous administration

IF 1 Q4 PHARMACOLOGY & PHARMACY
Pamela Huang BPharm, Carmela Corallo BPharm, Cherie Chiang MBBS (Hons), FRACP, FRCPA, MAACB, MD, FFSc, Yoke Chee Leong BSc, MAACB, Bianca Tong BPharm (Hons)
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引用次数: 0

Abstract

Background

Flucytosine is an antifungal agent used in combination with other medicines for the treatment of fungal infections. It was available as intravenous (IV), oral tablet, and capsule formulations up until October 2021, when the IV product, Ancotil, was discontinued with no alternative brands available.

Aim

This study aimed to formulate a suitable formulation with appropriate stability data for medium to long-term nasogastric (NG) administration use.

Method

Flucytosine 500 mg tablets (Ancotil) were crushed and suspended in (1) Ora-Plus (OP) + Ora-Sweet (OS) and (2) Ora-Blend (OB) to produce 100 mg/mL suspensions (n = 3 for each suspending base) that were stored at 2–8°C in amber glass bottles until assayed. Appearance, odour and pH, and the concentrations of flucytosine in the suspensions were determined by high-performance liquid chromatography on days 1, 8, and 15. A subjective assessment of the ease of suspension for NG administration via a size 10fr nasogastric tube (NGT) was also tested. Ethics approval was not required for this research article as it was a stability study and did not contain human participants or human data.

Results

One of the three OB suspension bottles demonstrated significant suspension clumping resulting in all OB suspensions being excluded from further analysis. There was no change in appearance, odour or pH with the OP + OS based flucytosine suspensions and they extruded easily through a size 10fr NGT with minimal force. The three OP + OS bottles of flucytosine suspension were stable (>98% at all timepoints assessed) for 15 days at 2–8°C when stored in amber glass bottles.

Conclusions

The OP + OS suspensions showed chemical stability for up to 15 days when stored under refrigerated conditions and protected from light, making this a suitable multidose enteral alternative to IV flucytosine.

氟胞嘧啶 100 毫克/毫升混悬液作为静脉注射替代品的稳定性
背景氟尿嘧啶是一种抗真菌药物,可与其他药物联合用于治疗真菌感染。该药有静脉注射剂、口服片剂和胶囊剂,直到 2021 年 10 月,静脉注射剂产品 Ancotil 停产,没有替代品牌。 目的 本研究旨在为中长期鼻胃(NG)给药配制一种具有适当稳定性数据的合适制剂。 方法 将氟尿嘧啶 500 毫克片剂(Ancotil)碾碎并悬浮于 (1) Ora-Plus (OP) + Ora-Sweet (OS) 和 (2) Ora-Blend (OB) 中,制成 100 毫克/毫升的悬浮液(每种悬浮基质 n = 3),在 2-8°C下贮存于琥珀色玻璃瓶中,直至化验。在第 1、8 和 15 天,用高效液相色谱法测定悬浮液的外观、气味和 pH 值以及氟西多辛的浓度。此外,还测试了悬浮液是否易于通过 10fr 大小的鼻胃管(NGT)进行 NG 给药的主观评估。由于这是一项稳定性研究,不涉及人类参与或人类数据,因此本研究文章无需获得伦理批准。 结果 三瓶转瓶混悬液中有一瓶出现了明显的混悬液结块现象,因此所有转瓶混悬液都被排除在进一步分析之外。基于 OP + OS 的氟尿嘧啶混悬液在外观、气味或 pH 值方面均无变化,而且它们很容易通过 10fr 的 NGT 管挤出,挤出力很小。三瓶 OP + OS 氟尿嘧啶混悬液在 2-8°C琥珀色玻璃瓶中储存 15 天后保持稳定(在所有评估的时间点均为 98%)。 结论 OP + OS 悬浮液在冷藏避光条件下保存 15 天后显示出化学稳定性,使其成为静脉注射氟尿嘧啶的合适多剂量肠内替代品。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Pharmacy Practice and Research
Journal of Pharmacy Practice and Research Health Professions-Pharmacy
CiteScore
1.60
自引率
9.50%
发文量
68
期刊介绍: The purpose of this document is to describe the structure, function and operations of the Journal of Pharmacy Practice and Research, the official journal of the Society of Hospital Pharmacists of Australia (SHPA). It is owned, published by and copyrighted to SHPA. However, the Journal is to some extent unique within SHPA in that it ‘…has complete editorial freedom in terms of content and is not under the direction of the Society or its Council in such matters…’. This statement, originally based on a Role Statement for the Editor-in-Chief 1993, is also based on the definition of ‘editorial independence’ from the World Association of Medical Editors and adopted by the International Committee of Medical Journal Editors.
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