Microbial Challenge of Stable Compounded Clozapine Suspensions in Plastic Bottles

Area of Science:

• Pharmaceutical Sciences
• Microbiology
• Clinical Pharmacy

Background:

• Clozapine oral suspension is not commercially available in Canada, necessitating compounded preparations for patients with swallowing difficulties.
• Existing stable clozapine suspension formulas lack documented evidence on the preservative system's efficacy against microbial contamination during use.

Purpose of the Study:

• To evaluate the antimicrobial effectiveness of 25-mg/mL and 50-mg/mL clozapine oral suspensions after 120 days of storage.
• To ensure compounded clozapine preparations can be provided to patients with confidence and support established beyond-use dates.

Main Methods:

• The study followed the USP Chapter <51> Preservative Effectiveness Test protocol for category 3 products.
• Clozapine suspensions (25 and 50 mg/mL) were stored for 120 days at 20-25°C in PET-G containers.
• Suspensions were inoculated with bacteria and fungi, incubated for 28 days, and microbial colony counts were assessed on days 7, 14, and 28.

Main Results:

• Initial microbial loads (10^5-10^6 CFU) declined to <10 CFU for bacteria and <30-50 CFU for yeast/fungi by day 7.
• Bacterial counts remained stable, while yeast and fungi counts further decreased to <10 CFU by days 14 and 28.
• These results demonstrate effective antimicrobial activity of the clozapine oral suspension.

Conclusions:

• Both 25-mg/mL and 50-mg/mL clozapine oral suspensions effectively control bacterial and fungal contamination per USP Chapter <51> standards.
• The formulation's stability, retaining >95% active concentration for 120 days at 4°C or 25°C, supports its clinical use.