Stability of Extemporaneously Compounded Tacrolimus in Glass Bottles and Plastic Syringes.

Tacrolimus is an immunosuppressive agent used to prevent allograph rejection.1,2 It is available as immediate-release (0.5-, 1-, and 5-mg) or extended-release (0.5-, 1-, 3-, and 5-mg) capsules. The stability of extemporaneous oral suspensions in Ora-Plus/Ora-Sweet and Ora-Plus/syrup has been reported previously.3-6The current study was undertaken to evaluate the stability of tacrolimus in Oral Mix vehicle. Tacrolimus suspensions (0.5 mg/mL) were prepared from bulk powder and from capsules. For bulk powder preparations, tacrolimus USP (117.6 mg; Medisca Pharmaceutique Inc, Montréal, Quebec; lot 48905/A, expiry May 2015; equivalent to 115 mg tacrolimus anhydrous) was wetted with polysorbate 80 (250 μL, Tween 80; Sigma Aldrich, Oakville, Ontario; lot MKBJ0197V) and Oral Mix vehicle (500 μL; Medisca Pharmaceutique Inc; lot I074/A, expiry February 2015) using a mortar and pestle. Oral Mix was then progressively added to achieve the required concentration (0.5 mg/mL, final volume 230 mL). Tacrolimus suspensions from capsules were similarly prepared, without polysorbate 80 (content of 23 × 5-mg Prograf capsules, Astellas Pharma Canada, Inc, Markham, Ontario; lot 044014, expiry April 2015; final volume 230 mL in Oral Mix). Each preparation was packaged in amber glass bottles (6 × 30-mL fill volume; 50-mL Wheaton type 1 bottles, Medisca Pharmaceutique Inc, lot 24908/A) and amber plastic syringes (48 × 1-mL fill volume; PreciseDose Dispenser, lot 46968/C, with tip cap, lot 55052/A, Medisca Pharmaceutique Inc). Preparations were stored at 5°C or 25°C for up to 90 days. Three bottles were stored at each temperature, and an aliquot was removed from each bottle at each time point for analysis. Half of the syringes were stored at each temperature, and 3 syringes per temperature were used for analysis on each study day. On each study day, all samples were examined for colour and odour, and pH was measured using a pH 211 meter (Hanna