Abstract
BACKGROUND: Clozapine oral suspension is not commercially available in Canada but is required for administration to patients who cannot swallow intact tablets. OBJECTIVE: To evaluate the stability of 25 mg/mL and 50 mg/mL clozapine suspensions prepared in a 50:50 mixture of methylcellulose gel 1% and Oral Syrup (flavoured syrup vehicle, Medisca Pharmaceutique Inc) and stored in amber glycol-modified polyethylene terephthalate (PET-G) bottles over 120 days at 4°C and 25°C. METHODS: This study used a validated reverse-phase stability-indicating liquid chromatographic method capable of quantifying clozapine, 3 known degradation compounds, a known impurity, and an unknown compound. Three separate batches of 25 mg/mL and 50 mg/mL clozapine suspensions were prepared, divided into 100-mL aliquots, and stored in 120-mL PET-G bottles. Half of the bottles from each concentration were stored at room temperature (20°C to 25°C) and the other half were stored in the refrigerator (2°C to 8°C). On study days 0, 28, 60, 90, and 120, concentrations of clozapine, each of the 3 known clozapine degradation products, a known impurity, and an unknown compound were determined. RESULTS: When suspensions were stored in PET-G containers at room temperature or under refrigeration for 120 days, the concentration of clozapine remained above 95% of initial concentration, and the measured concentration of degradation products and impurities did not exceed the 0.5% limits set by regulatory authorities worldwide. The proportion of the initial concentration of clozapine remaining on day 120, based on fastest degradation rate with 95% confidence (1-sided), exceeded 92%, and the only degradation product found (clozapine lactam, 0.2%) and an unknown impurity (0.2%) also did not exceed allowable limits. CONCLUSIONS: Compounded clozapine suspensions of 25 mg/mL and 50 mg/mL can be stored in amber PET-G containers for up to 120 days after preparation with storage at room temperature or under refrigeration.