ARTICLE Stability of Clozapine Stored in Oral Suspension Vehicles at Room Temperature

Rationale: For patients who cannot or will not take medications in tablet form, a liquid formulation of clozapine is required; however, no commercial oral liquid or suspension exists. Objective: To evaluate the stability of a 20 mg/mL clozapine suspension in 6 different suspending vehicles: Ora-Sweet, Ora-Plus, a 1:1 mixture of Ora-Sweet and Ora-Plus, the suspending vehicle used by the Hospital for Sick Children, simple syrup, and a noncommercial vehicle known as Guy’s pediatric mixture. Methods: A reverse-phase, stability-indicating liquid chromato-graphic method with ultraviolet detection at 230 nm was validated before the study. Validation demonstrated that clozapine could be quantified accurately and reproducibly. On study day 0, 100 mL of a 20 mg/mL clozapine suspension was prepared in each of the 6 suspending vehicles. Each suspension was separated into 3 equal aliquots, which were stored in 60-mL amber plastic containers. All suspensions were stored at room temperature (23°C) without protection from light. On study days 0, 3, 6, 14, 28, and 63, the concentration of clozapine was determined by liquid chromatography, and physical inspection was performed. Results: During the study period, all study samples retained more than 95.0 % of their initial concentration. Inspection of chromatograms obtained during the stability study failed to reveal any of the degradation products that had been generated during the assay validation. Conclusion: Suspensions of clozapine (20 mg/mL) prepared in the 6 suspending vehicles used in this study and stored in amber plastic containers at 23°C retained more than 95 % of their initial concentration during 63 days of storage, regardless of the suspending vehicle. Key words: drug stability, clozapine, suspensions, commercial suspending agent