Chemical Stability of Atomoxetine Hydrochloride and Fluoxetine Hydrochloride Oral Anhydrous Extemporaneously Compounded Suspensions.

Abstract

Objective: Atomoxetine is indicated for the treatment of attention-deficit/hyperactivity disorder, and fluoxetine is commonly used for treating depression. Variable dosing per body weight is required in children, and the commercially available capsules do not offer the required flexibility and potential for customization. The objective of this study was to evaluate the physicochemical stability of atomoxetine hydrochloride and fluoxetine hydrochloride oral anhydrous extemporaneously compounded suspensions.

Methods: An anhydrous suspension of atomoxetine hydrochloride was prepared from commercially available capsules at a 4-mg/mL concentration, and an anhydrous suspension of fluoxetine hydrochloride was prepared from pure drug powder at a concentration of 10 mg/mL. The extemporaneously compounded suspensions were prepared according to standardized formulas and methods of preparation. Samples were stored at refrigerated and controlled room temperatures for 6 months. The physicochemical properties of the samples were analyzed and characterized on days 0, 14, 30, 60, 90, and 180. A robust stability-indicating ultra-performance liquid chromatography assay method was validated and employed.

Results: The samples remained consistent in appearance and color, with atomoxetine forming a pale-yellow suspension and fluoxetine yielding an off-white to faint beige suspension. Both anhydrous suspensions remained within the ±10% potency specification. The percent concentration relative to labelled concentration (potency) was at or above 96.5% for atomoxetine and at or above 96.8% for fluoxetine.

Conclusion: Beyond-use dates of 6 months at both refrigerated and room temperature conditions have been established for the atomoxetine 4-mg/mL anhydrous suspension and the fluoxetine 10-mg/mL anhydrous suspension.