(W1030-07-42) Long-Term Stability Studies of Extemporaneously Compounded Amiloride Nasal Spray

Purpose: Pre-clinical data indicates that intranasally administered amiloride has the potential to provide rapid relief of symptomatic anxiety. Amiloride is a potassium-sparing diuretic that decreases anxiety by inhibiting acid-sensing ion channels. In previous work, the microbiological, chemical, and physical stability of compounded amiloride nasal spray were verified at 3 hours, 24 hours, and 7 days (1). This study reports the estimated long-term chemical and physical stability of extemporaneously compounded 2 mg/ml Amiloride nasal spray under accelerated environmental conditions at 6 and 12 months.

Methods: A stability-indicating analytical method developed in a previous study was used to detect and quantify amiloride in the nasal spray samples (1). The nasal spray was prepared as previously reported except with the modification of adding the amiloride to bacteriostatic water containing 0.9% benzyl alcohol, rather than to sterile water for injection. This was done to impart an extended microbiological stability to the nasal spray. This solution was stored for one month at 60° C in a stability chamber. At time points 0, 2, and 4 weeks, samples were withdrawn for chemical and physical stability analysis. The percent amiloride remaining was calculated and extrapolated representing day 0, 6 months, and 12 months using the Arrhenius equation to estimate the effect of temperature on amiloride degradation. Additionally, the samples were tested for physical stability (color, turbidity, and pH) at each time point.

Results: The preservative benzyl alcohol did not co-elute with amiloride when samples were analyzed with the stability-indicating analytical method. All tested solutions retained over 90% of the initial amiloride concentration at the measured time points and by extrapolation, at 6 and 12 months (Table 1). There were no significant changes in color or turbidity observed. It was found that the pH decreased over time, likely due to the exposure of the solution to the high temperature.

Conclusion: Extemporaneously compounded 2 mg/ml amiloride nasal spray was chemically stable for an estimated 12 months when stored under accelerated conditions. The solution also retained physical stability in terms of color and turbidity when stored under accelerated conditions. Although pH decreased over time, this could be attributed to the high heat of accelerated storage conditions.

References: 1. Yellepeddi V, Sayre C, Burrows A, Watt K, Davies S, Strauss J, et al. Stability of extemporaneously compounded amiloride nasal spray. PLoS One. 2020;15(7):e0232435.

Table 1. Stability of 2 mg/mL amiloride nasal spray solution