Background Pharmaceutical industry does not always provide suitable preparations for paediatric population. In these situations formulations should be developed for small scale compounding in hospital pharmacies, especially when cytotoxic drugs are involved.
Purpose Some guidelines for non-sterile pharmaceutical compounding preparations (eg, USP797) recommends in absence of stability information, an expiry date of 14 days under refrigeration for liquid preparations. The aim of the study is to develop a methotrexate oral formulation that yields stable for at least 25 days, an adequate period for three weekly administrations of one chemotherapy cycle.
Materials and methods Two formulations of 2.5 mg/ml were prepared by dissolving respectively tablets or injectable solution of methotrexate with Ora-Plus and Ora Sweet SF mixed in a 1:1 ratio. Preparations packed in amber coloured bottles were kept at 2-8° C. Samples were taken at 1, 7, 15, 25 days, and were analysed for appearance, pH, microbiological growth and methotrexate concentrations by Fluorescense Polarisation Immunoassay (FPIA) and ultraviolet-visible spectroscopy (UV-S) at 370 nm only with the solution (no supported for suspensions). Assays were specific for methotrexate (without cross-reactivity with metabolites) and calibrated with a known concentration. A stability study has been performed on these two formulations. Samples were diluted 1/100 with Xsystems Dilution Buffer. In FPIA was also performed the 1:100 dilution protocol of TDx/TDxFLx analyser.
Results Both formulations show stability for at least 25 days, with remaining content of methotrexate of 98.76% in suspension and 97.06% (FPIA) or 96.20% (UV-S) in solution. Appearance assay (no odour or colour changes), pH (5.0) and microbiological growth (negative) in all samples were appropriate and similar for both formulations.
Conclusions Methotrexate can be extemporaneously prepared in suspension or solution and stored at least 25 days under refrigeration without significant degradation. For paediatric patients who cannot swallow tablets, these formulations provide an accurate and suitable option for administering oral methotrexate.
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