Physicochemical and Microbiological Stability of Compounded Metronidazole Suspensions in PCCA SuspendIt.

Metronidazole is indicated for the treatment of trichomoniasis, amebiasis, and anaerobic bacterial infections. The dosage regimen of metronidazole needs to be individualized in the treatment of trichomoniasis, in patients with hepatic impairment, and in pediatric as well as geriatric patients. A review of the therapeutic uses of metronidazole reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of metronidazole currently exists. Metronidazole is commercially available only as 250-mg and 500-mg film-coated tablets. An extemporaneously compounded suspension from pure drug powder or commercial tablets would provide a convenient option to meet unique patient needs. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded metronidazole suspensions in PCCA SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two metronidazole concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating ultra-performance liquid chromatographic assay for the determination of the chemical stability of metronidazole in PCCA SuspendIt was developed and validated. Suspensions of metronidazole were prepared in PCCA SuspendIt at 25-mg/mL and 50-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in plastic amber prescription bottles at two temperature conditions (5AEC and 25AEC). Samples were assayed initially and on the following time points (days): 7, 14, 28, 42, 59, 90, 122, and 180. Physical data such as pH, viscosity, and appearance were also noted. Microbiological stability was also tested. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. The study showed that metronidazole concentrations did not go below 97% of the label claim (initial drug concentration) at both temperatures studied. No microbial growth was observed. Viscosity and pH values also did not change significantly. This study demonstrates that metronidazole is physically, chemically, and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for metronidazole in a liquid dosage form, with an extended beyond-use-date to meet patient needs.