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

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.