An Evaluation of Amoxicillin/Clavulanate Stability in Aqueous Systems, Including Its Suitability for Outpatient Parenteral Antimicrobial Therapy (OPAT).

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2024-09-24 eCollection Date: 2024-01-01 DOI:10.2147/DDDT.S474850

Kamrin Kamalpersad, Giuseppe Luna, Bruce Sunderland, Petra Czarniak

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Abstract

Purpose: Amoxicillin/clavulanate antibiotic combination is suitable for treating a range of infections, including some suited for Outpatient Parenteral Antimicrobial Therapy (OPAT). The aim of the study was to evaluate shelf-life values of amoxicillin at clinical concentrations in the presence of clavulanate for use in OPAT.

Methods: A stability-indicating HPLC assay was developed and validated. Kinetic studies were performed at 1 mg/mL and 15 mg/mL amoxicillin at 40-60 °C. Studies in elastomeric infusers included the pH lowered from 8.73 to 6.52 for 1 mg/mL; 8.85 to 7.69 for 7.5 mg/mL and 8.68 to 8.40 for 15 mg/mL amoxicillin plus clavulanate and stored at 2.9 °C.

Results: Amoxicillin and clavulanate eluted at 5.2 and 3.0 minutes, respectively, with linear concentration relationships. Forced degradation retained base-line separation of each component in the presence of degradation products. Amoxicillin 1 mg/mL had a shelf-life of 4.85 hours at pH 6.53 and 40 °C which on extrapolation to 25 °C was 22.8 h. Clavulanate was 1.38 h at 40 °C and 4.0 h at 25 °C. Amoxicillin 15 mg/mL at pH 8.34 gave a shelf-life of 0.11 h at 40 °C and clavulanate 0.41 h. In elastomeric infusers, amoxicillin 1 mg/mL, with lowering pH from 8.73 to 6.52, improved the shelf-life at 2.9 °C from 72 to >263.8 h and similarly for clavulanate. At 7.5 mg/mL amoxicillin, lowering pH from 8.85 to 7.69 improved the shelf-life from 4.2 to 51.8 h and clavulanate from 4.2 to 48.0 h. At 15 mg/mL amoxicillin, the shelf-life values at pH 8.68 or 8.40 were 3.8 h and 1.6 h and similarly for clavulanate.

Conclusion: Amoxicillin and clavulanate showed adequate stability at 2.9 °C for OPAT storage at 1 mg/mL and possibly 7.5 mg/mL, but not 15 mg/mL. Low shelf-life values at 25 °C also limit administration times.

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评估阿莫西林/克拉维酸在水性体系中的稳定性，包括其是否适合门诊患者肠外抗菌治疗 (OPAT)。

目的：阿莫西林/克拉维酸复合抗生素适用于治疗一系列感染，包括一些适合门诊肠外抗菌疗法（OPAT）的感染。本研究旨在评估阿莫西林在克拉维酸存在的临床浓度下用于 OPAT 的保质期值：方法：开发并验证了一种稳定性指示高效液相色谱法。在 40-60 °C、1 毫克/毫升和 15 毫克/毫升阿莫西林浓度下进行了动力学研究。在弹性输液器中进行的研究包括：1 毫克/毫升阿莫西林的 pH 值从 8.73 降至 6.52；7.5 毫克/毫升阿莫西林的 pH 值从 8.85 降至 7.69；15 毫克/毫升阿莫西林加克拉维酸的 pH 值从 8.68 降至 8.40，并储存在 2.9 ℃：阿莫西林和克拉维酸分别在 5.2 分钟和 3.0 分钟洗脱，浓度呈线性关系。在存在降解产物的情况下，强制降解保持了每种成分的基线分离。阿莫西林 1 毫克/毫升在 pH 值为 6.53、温度为 40 ℃ 时的保质期为 4.85 小时，推算到 25 ℃ 时为 22.8 小时；克拉维酸在 40 ℃ 时为 1.38 小时，在 25 ℃ 时为 4.0 小时。在弹性输液器中，阿莫西林 1 毫克/毫升，pH 值从 8.73 降到 6.52 时，在 2.9 °C 下的保存期从 72 小时延长到大于 263.8 小时，克拉维酸也是如此。在 7.5 毫克/毫升阿莫西林中，pH 值从 8.85 降至 7.69 时，保质期从 4.2 小时延长至 51.8 小时，克拉维酸盐则从 4.2 小时延长至 48.0 小时：阿莫西林和克拉维酸钾在 2.9 °C、1 毫克/毫升或 7.5 毫克/毫升、15 毫克/毫升的 OPAT 储存条件下具有足够的稳定性。25 °C下的低保质期值也限制了给药时间。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.