Stability of Captisol-enabled versus propylene glycol-based melphalan at room temperature and after refrigeration

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Purpose: To compare the chemical stability of Captisol-enabled (CE) melphalan ("CE-melphalan"; Evomela, Acrotech Biopharma LLC) and propylene glycol-(PG)-based melphalan ("PG-melphalan"; Alkeran, GlaxoSmithKline) admixtures prepared with 0.9% sodium chloride injection in polyvinyl chloride (PVC) bags or reconstituted vials stored at room temperature (RT) and under refrigeration.

Methods: Lyophilized CE-melphalan and generic PG-melphalan were reconstituted to 5 mg/mL with 0.9% sodium chloride injection or manufacturer-supplied diluent, respectively. The reconstituted vials were then diluted to the desired concentrations with 0.9% sodium chloride injection in PVC bags and were stored at RT (23 °C) or under refrigeration (4 °C). Aliquots were withdrawn from the bags and reconstituted vials of CE-melphalan and PG-melphalan immediately after preparation and at predetermined time intervals. Melphalan concentrations were measured using a validated high-performance liquid chromatography method.

Results: CE-melphalan reconstituted in PVC bags at concentrations of 1 and 2 mg/mL was stable for 6 and 24 hours, respectively, at RT and for 8 and 24 hours, respectively, at 4 °C. PG-melphalan reconstituted in bags at 1, 1.5, and 2 mg/mL was stable for 1, 2, and 2 hours, respectively, at RT and for 2, 4, and 4 hours, respectively, at 4 °C. Reconstituted CE-melphalan vials were stable for 48 hours at both RT and 4 °C, whereas PG-melphalan vials were stable for 6 hours at RT but formed precipitate within 2 hours at 4 °C.

Conclusion: CE-melphalan remained stable longer than generic PG-melphalan under the test conditions. CE-melphalan at 2 mg/mL has 24-hour stability at RT and can be used for extended infusion times or may be compounded ahead of time. Reconstituted CE-melphalan vials are stable for 48 hours at both RT and 4 °C.

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