Stability of Compounded Clozapine 25 mg/mL and 50 mg/mL Suspensions in Plastic Bottles.

Abstract

Clozapine oral suspension is not commercially available in Canada but is required for administration to patients who cannot swallow intact tablets. 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. 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. 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. 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.