Microbial Challenge of Stable Compounded Clozapine Suspensions in Plastic Bottles

Author(s):  Berzy Jessica, Sachedina Hanif, Virji Arif, Gross Jason A, Cull Erica, Walker Scott E

Issue:  May/Jun 2025 - Volume 29, Number 3
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Abstract:  Background and Rationale: A clozapine oral suspension is not commercially available in Canada and is required for administration to patients who cannot swallow intact tablets. While a stable formula has been described, no studies document the effectiveness of the preservative system used in this formulation to control inadvertent microbial contamination by the user during use of the preparation. Objective: The objective of this study was to evaluate the antimicrobial effectiveness of 25-mg/mL and 50-mg/mL oral suspension of clozapine after 120-days of storage at 20o-25oC, ensuring a compounded clozapine preparation can be provided to a patient with confidence and supporting the beyond-use-date of the preparation. Methods: The USP Chapter <51> Preservative Effectiveness Test protocol was followed as described for category 3 products. After storage for 120-days at 20o-25oC in amber glycol-modified polyethylene terephthalate (PET-G), both the 25-mg/mL and 50-mg/mL clozapine suspensions were inoculated with 3 different strains of bacteria and 2 strains of fungi and incubated for 28-days. On days 7, 14 and 28, the bacterial and fungal colony counts determined the antimicrobial effectiveness of the suspension. The suitability of the microbial recovery method was validated prior to completing the challenge test. Results: The microbial load of the clozapine suspensions declined from an initial CFU count between 105-106 to less than 10-CFU by day 7 for bacteria and less than 30-50 CFU for yeast & fungi. On days 14 and 28, the bacteria showed no changes from counts at day 7th, while the yeast & fungi declined to less than 10 CFU. This indicates effective antimicrobial activity of the clozapine oral suspension. Conclusions: The 25-mg/mL and 50-mg/mL clozapine suspensions have been demonstrated to effectively control bacterial and fungal contamination, as judged by the USP Chapter <51> Antimicrobial Effectiveness Test. This bracketed formulation has been previously demonstrated to retain more than 95% of its initial active concentration when stored at 4oC or 25oC for 120-days.

Related Categories: PACKAGING, STABILITIES, COMPATIBILITIES, STERILE PREPARATIONS, STORAGE

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