In Vitro Assessment for Dose Preparation and Simulated Administration of Azithromycin Suspensions via Enteral Feeding Tubes

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.