Background and Importance Tacrolimus is an immunosuppressive agent used in solid organ transplantation (SOT) for prophylaxis of rejection. In our hospital SOT are performed including rare multivisceral transplantations (MTVx). There are clinical situations when oral tacrolimus can not be administered to the MTVx patient because of a non-functional bowel. In home care, patient could be treated with tacrolimus for sublingual use. There is no commercial product for sublingual administration available, so formulation has to be developed.
Tacrolimus is practically insoluble in water; however, suspension can be prepared using tacrolimus capsule powder content. This formulation is unstable with risk of sedimentation, therefore uniform dose can not be achieved. We used solubility of tacrolimus in ethanol and prepared the homogenous sublingual solution from substance.
Aim and Objectives To formulate solution of tacrolimus 10 mg/mL based on ethanol and glycerol. To describe the preparation, container, storage conditions and shelf-life of tacrolimus solution for sublingual use.
Material and Methods Tacrolimus belongs to hazardous drugs, H 361. Biological safe cabinet (BSC) is recommended for tacrolimus preparation.
Solution was prepared using the glass beaker and stick. Tacrolimus was dissolved in ethanol 96%, then glycerol 85% was slowly added. The citric acid was used to adjust pH 5-6, optimal for stability of tacrolimus. Orange flavour was added for higher palatability. The amber glass container with adapter for oral syringe was used.
Results Turbid and homogenous solution with orange scent and pH 6 was obtained. Concentration of tacrolimus was 10 mg/mL. Shelf-life of 30 days was given, stored in 15°C–25°C according to the USP <795>. Oral dosing syringe was used to apply the sublingual solution.
Conclusion and Relevance The formulation of tacrolimus was developed. Variety of concentrations of tacrolimus solution may be prepared. This allows us to prepare solution with higher concentration with the same volume, if needed. Our MTVx patient had a good tolerance to this solution. He has taken this solution since November 2021 and has remained stable without rejection of transplanted stomach, liver and pancreas.
It is necessary to work fast, because of an air flow in BSC, the ethanol evaporates and the solution may precipitate. Clinical effectiveness might be investigated to confirm the utility of this formulation.
Conflict of Interest No conflict of interest
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