Long‐term stability of tacrolimus in compounded oral suspensions and ointment

Abstract Background Tacrolimus is a potent immunosuppressant that is widely used to treat various inflammatory or immunity‐mediated diseases and prevent organ transplant rejection. Although tacrolimus is commercially available in 0.5 mg, 1 mg, and 5 mg capsules for oral administration, no registered liquid or semi‐solid dosage of tacrolimus exists in Australia. Currently, demand for tacrolimus suspensions and ointments is fulfilled by compounded formulations prepared by compounding pharmacies. Aim This research aimed to develop and validate a stability‐indicating high‐performance liquid chromatography (HPLC) method to determine tacrolimus in different formulations and then assessed the long‐term stability of tacrolimus in suspensions (1 mg/mL) prepared in Oral Mix, SF (sugar‐free) (OM), Ora‐Blend SF (sugar‐free) (OB), and ointment (0.1%) in petrolatum when stored at controlled room temperature for 12 months. Method The analytical performance parameters of the developed HPLC assay, comprising selectivity, specificity, linearity, accuracy, and precision, were evaluated according to the International Conference on Harmonisation (ICH) Q2(R1) guidelines. Tacrolimus concentration, drug breakdown research, pH, colour, and odour were assessed over a 12‐month period in suspensions and ointment. Ethics approval was not required for this research article as it was a stability study and did not contain human participants or data. Results The HPLC assay method was found to be precise for quantification of tacrolimus in oral suspensions and onitment. The tacrolimus suspensions based on OM or OB exhibited no alteration in appearance, pH, or odour over the 12‐month study period. Both tacrolimus suspensions retained ≥93% of the initial concentration over 12 months at room temperature. The ointment formulation maintained a tacrolimus content of ≥92% for the 12‐month duration. Conclusion Both tacrolimus suspensions and ointment formulations demonstrated physical and chemical stability for up to one year, for samples that were kept under room temperature conditions.