Background Cyclosporine is an immunosuppressive drug known for its narrow therapeutic range. The only formulation available on the market offers a concentration of 100 mg/mL. However, in our hospital, the paediatric department regularly requires dosages as low as 4 mg that are difficult to prepare from the pharmaceutical specialty. This may lead to inaccurate doses that can have a marked clinical impact. In this context, we developed a 10 mg/mL cyclosporine formulation.
Purpose The aim of this study was to determine the physicochemical stability of our 10 mg/mL cyclosporine formulation, to establish the shelf-life.
Material and methods Initially, we developed a stability indicating method. We assessed the accuracy, repeatability and linearity of the procedure. We also characterised the degradation products. The concentrations were assessed by high performance liquid chromatography-UV detection method using a Xterra RP18 150x4.6mm-5 µm column. The mobile phase used was acetonitrile/water, 70/30. We then prepared three batches of solution, using cyclosporine powder and olive oil, complying with the European Pharmacopoeia. We used alpha-tocopherol as an antioxidant. All three batches were packaged in amber vials to protect from light and stored at room temperature. Several parameters where monitored on different days (0, 1, 4, 10, 14, 30): physical stability (visual inspection) and chemical stability (cyclosporine residual concentration and degradation product detection).
Results After 30 days, no concentration variations were observed. All three batches showed cyclosporine concentration variation of <5%, which is considered acceptable based on ICH recommendations. No degradation products were detected throughout the study. No macroscopic alteration was observed. However, microbiological stability was not assessed. This parameter will be evaluated in further studies.
Conclusion This study showed that 10 mg/mL cyclosporine oral solution in olive oil was stable for at least 30 days at room temperature and protected from light. Therefore, we can set a shelf-life of 30 days. This 10 mg/mL cyclosporine solution will provide an interesting alternative to the pharmaceutical specialty to administer more accurate cyclosporine doses to paediatric patients.
References and/or acknowledgements http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q1A_R2/Step4/Q1A_R2__Guideline.pdf
No conflict of interest
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