TY - JOUR
T1 - Stability of Captisol-enabled versus propylene glycol-based melphalan at room temperature and after refrigeration
AU - Kawedia, Jitesh D.
AU - Ramchandran, Sumankalai
AU - Liu, Xiaoqian
AU - Gulbis, Alison M.
AU - Titus, Mark
AU - Bashir, Qaiser
AU - Qazilbash, Muzaffar H.
AU - Champlin, Richard E.
AU - Ciurea, Stefan O.
N1 - Publisher Copyright:
© 2022 American Society of Health-System Pharmacists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2022/6/15
Y1 - 2022/6/15
N2 - 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 (23oC) or under refrigeration (4oC). Aliquots were withdrawn from the bags and reconstituted vials of CE-melphalan and PG-melphalan immediately after preparation and at predetermined time intervals.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 4oC. 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 4oC. Reconstituted CE-melphalan vials were stable for 48 hours at both RT and 4oC, whereas PG-melphalan vials were stable for 6 hours at RT but formed precipitate within 2 hours at 4oC. 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 4oC.
AB - 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 (23oC) or under refrigeration (4oC). 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 4oC. 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 4oC. Reconstituted CE-melphalan vials were stable for 48 hours at both RT and 4oC, whereas PG-melphalan vials were stable for 6 hours at RT but formed precipitate within 2 hours at 4oC. 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 4oC.
KW - Alkeran
KW - Captisol-enabled melphalan
KW - drug stability
KW - Evomela
KW - hematopoietic stem cell transplantation
KW - propylene-glycol melphalan
UR - http://www.scopus.com/inward/record.url?scp=85131701895&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85131701895&partnerID=8YFLogxK
U2 - 10.1093/ajhp/zxac055
DO - 10.1093/ajhp/zxac055
M3 - Article
C2 - 35176751
AN - SCOPUS:85131701895
SN - 1079-2082
VL - 79
SP - 1011
EP - 1018
JO - American Journal of Health-System Pharmacy
JF - American Journal of Health-System Pharmacy
IS - 12
ER -