Santangelo Matthew, Wood Julia A, Barnett Kimber L, Wooding Fae Gwen G, Bartlett Jeremy A
Pfizer Inc., Groton, CT, USA.
Pfizer Inc., Andover, MA, USA.
Hosp Pharm. 2022 Apr;57(2):260-267. doi: 10.1177/00185787211024216. Epub 2021 Jun 11.
Administration of medication via enteral feeding tubes (EFT) is common in cases where patients are unable to swallow the dosage form or a patient is intubated. The SARS-CoV-2 (COVID-19, coronavirus disease 2019) epidemic created a need to rapidly evaluate potential treatment options to address the global pandemic including evaluation of azithromycin (AZM) as a mono or combination therapy. Due to the complicating medical conditions of COVID-19, in some cases patients may be unable to take medication orally and could require medication administration by alternate routes such as an EFT. The aim of this study was an in vitro assessment for the dose preparation and simulated administration of AZM suspensions, prepared from tablets and capsules, via nasogastric feeding tubes (NGT). AZM tablets and capsules were used to prepare aqueous suspensions from 250 to 2000 mg for administration via NGT. NGT between 8 and 12 French (Fr), from common materials of construction and typical lengths were evaluated. About 20 mL syringes were used with water as the diluent. The preparation and simulated NGT administration steps for AZM suspensions were evaluated in the laboratory studies and included assessment of in-use stability of the aqueous suspensions, chemical compatibility of prepared aqueous suspensions with the syringe and NGT, ease of delivery and accuracy of simulated administration. Analysis of the prepared sample solutions for assay/impurities was performed using chromatographic conditions based on the USP-NF monograph. Verification of dose preparation and simulated administration was performed for intact tablets, crushed tablets, and capsules. Aqueous suspensions prepared from intact tablets and capsules were exposed to dosing materials (enteral syringe and NGT) for a period of up to 4 hours at ambient conditions. Assessment of the ease of dose delivery and analyses of the resulting samples for assay, purity and total degradation products were performed. The laboratory studies verified a procedure to reliably prepare suspensions from AZM tablets and capsules, over a range of 250 to 2000 mg, that can be accurately administered through NGT in sizes of 8 to 12 Fr. No incompatibilities of the prepared aqueous AZM suspension with dosing materials were observed and acceptable stability was demonstrated for up to 4 hours.
对于无法吞咽剂型或已插管的患者，通过肠内喂养管（EFT）给药很常见。严重急性呼吸综合征冠状病毒2（SARS-CoV-2，即2019冠状病毒病）疫情使得有必要迅速评估潜在的治疗方案以应对全球大流行，包括评估阿奇霉素（AZM）作为单一疗法或联合疗法。由于COVID-19患者存在复杂的医疗状况，在某些情况下，患者可能无法口服药物，可能需要通过鼻胃管（NGT）等替代途径给药。本研究的目的是对由片剂和胶囊制备的AZM混悬液通过鼻胃管进行剂量制备和模拟给药的体外评估。使用AZM片剂和胶囊制备浓度为250至2000mg的水性混悬液，通过NGT给药。评估了8至12法式（Fr）、由常见建筑材料制成且长度典型的NGT。使用约20mL注射器，以水作为稀释剂。在实验室研究中评估了AZM混悬液的制备和模拟NGT给药步骤，包括评估水性混悬液的使用稳定性、制备的水性混悬液与注射器和NGT的化学相容性、给药的难易程度以及模拟给药的准确性。使用基于美国药典-国家处方集专论的色谱条件对制备的样品溶液进行含量测定/杂质分析。对完整片剂、压碎片剂和胶囊进行剂量制备和模拟给药验证。由完整片剂和胶囊制备的水性混悬液在环境条件下与给药材料（肠内注射器和NGT）接触长达4小时。评估给药的难易程度，并对所得样品进行含量测定、纯度和总降解产物分析。实验室研究验证了一种从AZM片剂和胶囊可靠制备混悬液的方法，混悬液浓度范围为250至2000mg，可通过8至12Fr的NGT准确给药。未观察到制备的AZM水性混悬液与给药材料之间存在不相容性，并且在长达4小时内显示出可接受的稳定性。
