Stability study of extemporaneously compounded nitrofurantoin oral suspensions for pediatric patients

Abstract

Aim: To evaluate the stability of nitrofurantoin suspended in different extemporaneously compounded vehicles after storage at 4°C and at 25°C. To formulate an effective, readily available vehicle that can guarantee extended stability and precise dosing. Materials and methods: Nitrofurantoin was suspended at a concentration of 10 mg/mL in seven different vehicles compounded of different blends of Syrupus simplex, sorbitol 70%, methylcellulose 1%, gummi arabici 1%, gummi xanthani 1%, and sodium carboxymethylcellulose (NaCMC) 1%. Samples of 100 mL of every compounded suspension were stored in dark in graded glass bottles at 4°C and at 25°C. Samples were analyzed at the beginning and every 10 days up to day 30 and every 30 days after. Variations of physical properties such as sedimentation, ease of resuspension, color and odor were evaluated visually and organoleptically. Rheological analysis was also performed in order to determine suspensions’ behavior during storage and dosing. Variations in nitrofurantoin concentration and pH were evaluated with suitable analytical procedure (UV-Vis; HPLC; pH/ORP). Microbiological stability was evaluated via incubation on suitable culture media. Results: To the 30th day, only three of the compounded suspensions exhibited significant physical stability and slight change in taste and odor stored at both temperatures. Two samples stored at 25°C exhibited nitrofurantoin concentration greater than 95% and 4 samples stored at 4°C – concentration greater than 95%. All models showed no microbial growth up to day 30. At 120 days, only three of the compounded suspensions, stored at 4°C, exhibited relatively high nitrofurantoin concentrations: 88.2%, 92%, and 81.1%, respectively. Only one model suspension showed chemical and physical stability (≥95% of the initial concentration) for 102 days. No model suspension remained sterile after 30 days. Conclusions: The suspensions compounded with vehicles of blends of syrups, xanthan, croscarmellose (NaCMC), and sorbitol exhibited low to none sedimentation, good uniformity of content and are suitable organoleptically for pediatric administration. The model suspension stored at 4°C (NTF VII 4°C – with major excipients: sucrose 16%, sorbitol 17%, xanthan gum 0.25%, NaCMC 0.25%) stands out with nitrofurantoin concentration higher than 95% along with no or little signs of sedimentation. After adding a suitable preservative agent or system, a formulation with these characteristics might have an expiration date of at least 90 days.

Potential of Nitrofurantoin Cyclodextrin Nanosponge Complex to Enhance Solubility and Masking Bitter Taste

“…Patients may find it difficult to take nitrofurantoin due to its bitter taste, especially young patients and older patients who may have trouble swallowing tablets or suspensions. 11 The bitter taste of nitrofurantoin can be lessened or covered by using a variety of techniques to solve this problem.…”