Stability of 25 mg/mL Azacitidine Suspensions Kept in Fridge after Freezing
Azacitidine is supplied as lyophilized powder to be reconstituted with sterile water for injection. The molecule is very unstable in aqueous medium (temperature-dependent process). Advance preparation and leftover management are made difficult by such poor stability. This study evaluates the stabili...
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Online Access: | https://doi.org/10.1515/pthp-2016-0023 |
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doaj-91c67b02eff64ebe8ce7dba5f624b1cc2021-10-02T19:03:44ZengDe GruyterPharmaceutical Technology in Hospital Pharmacy2365-24112365-242X2017-03-0121111610.1515/pthp-2016-0023Stability of 25 mg/mL Azacitidine Suspensions Kept in Fridge after FreezingBalouzet Clara0Chanat Cédric1Jobard Marion2Brandely-Piat Marie-Laure3Chast François4Clinical Pharmacy Department, Paris University Hospital Hôtel Dieu, AP-HP, Paris, FranceClinical Pharmacy Department, Paris University Hospital Hôtel Dieu, AP-HP, Paris, FranceClinical Pharmacy Department, Paris University Hospital Hôtel Dieu, AP-HP, Paris, FranceClinical Pharmacy Department, Paris University Hospital Hôtel Dieu, AP-HP, Paris, FranceClinical Pharmacy Department, Paris University Hospital Hôtel Dieu, AP-HP, Paris, FranceAzacitidine is supplied as lyophilized powder to be reconstituted with sterile water for injection. The molecule is very unstable in aqueous medium (temperature-dependent process). Advance preparation and leftover management are made difficult by such poor stability. This study evaluates the stability of 25 mg/mL azacitidine suspensions kept for a 1-month period at –20 °C, followed by a 5-day period at 5 °C. Three batches of 7 polypropylene syringes were filled with 2 mL of Vidaza® (Celgene, France) reconstituted with cold sterile water for injection: 1 syringe was immediately analysed, the other 6 were stored at –20 °C. After 1 month, the 6 syringes were defrosted at room temperature (20 min) and then stored in a refrigerator at 2–8 °C. Experimental timings were determined as follows: preparation day (Dfab), defrosting day (D0) and every 24 h for the following 5 days (from D1 to D5). Several types of analyses were carried out: visual inspections, microscopic observations of crystal shape, turbidity measurements (UV-visible spectrophotometry) and UV-HPLC analyses (stability assessment method adapted from Harting et al). The ICH Guidelines’ specifications of 5 % change were retained. At D0, after 1 month at –20 °C, the volume contained in the syringes showed an increase (+5 %), and a phase separation, reversible by strong agitation, was observed. From the microscopic point of view, crystals appeared to be larger at D5 than at D0. With regard to content, average losses of 4.5 % at D3 and 8.3 % at D5 were observed. Freezing efficiently prevents azacitidine from degrading. Advance preparation of 25 mg/mL azacitidine syringes can therefore be achieved provided they are immediately frozen at –20 °C and then stored at 5 °C for 3 days.https://doi.org/10.1515/pthp-2016-0023azacitidinestabilityfreezingadvance preparation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Balouzet Clara Chanat Cédric Jobard Marion Brandely-Piat Marie-Laure Chast François |
spellingShingle |
Balouzet Clara Chanat Cédric Jobard Marion Brandely-Piat Marie-Laure Chast François Stability of 25 mg/mL Azacitidine Suspensions Kept in Fridge after Freezing Pharmaceutical Technology in Hospital Pharmacy azacitidine stability freezing advance preparation |
author_facet |
Balouzet Clara Chanat Cédric Jobard Marion Brandely-Piat Marie-Laure Chast François |
author_sort |
Balouzet Clara |
title |
Stability of 25 mg/mL Azacitidine Suspensions Kept in Fridge after Freezing |
title_short |
Stability of 25 mg/mL Azacitidine Suspensions Kept in Fridge after Freezing |
title_full |
Stability of 25 mg/mL Azacitidine Suspensions Kept in Fridge after Freezing |
title_fullStr |
Stability of 25 mg/mL Azacitidine Suspensions Kept in Fridge after Freezing |
title_full_unstemmed |
Stability of 25 mg/mL Azacitidine Suspensions Kept in Fridge after Freezing |
title_sort |
stability of 25 mg/ml azacitidine suspensions kept in fridge after freezing |
publisher |
De Gruyter |
series |
Pharmaceutical Technology in Hospital Pharmacy |
issn |
2365-2411 2365-242X |
publishDate |
2017-03-01 |
description |
Azacitidine is supplied as lyophilized powder to be reconstituted with sterile water for injection. The molecule is very unstable in aqueous medium (temperature-dependent process). Advance preparation and leftover management are made difficult by such poor stability. This study evaluates the stability of 25 mg/mL azacitidine suspensions kept for a 1-month period at –20 °C, followed by a 5-day period at 5 °C. Three batches of 7 polypropylene syringes were filled with 2 mL of Vidaza® (Celgene, France) reconstituted with cold sterile water for injection: 1 syringe was immediately analysed, the other 6 were stored at –20 °C. After 1 month, the 6 syringes were defrosted at room temperature (20 min) and then stored in a refrigerator at 2–8 °C. Experimental timings were determined as follows: preparation day (Dfab), defrosting day (D0) and every 24 h for the following 5 days (from D1 to D5). Several types of analyses were carried out: visual inspections, microscopic observations of crystal shape, turbidity measurements (UV-visible spectrophotometry) and UV-HPLC analyses (stability assessment method adapted from Harting et al). The ICH Guidelines’ specifications of 5 % change were retained. At D0, after 1 month at –20 °C, the volume contained in the syringes showed an increase (+5 %), and a phase separation, reversible by strong agitation, was observed. From the microscopic point of view, crystals appeared to be larger at D5 than at D0. With regard to content, average losses of 4.5 % at D3 and 8.3 % at D5 were observed. Freezing efficiently prevents azacitidine from degrading. Advance preparation of 25 mg/mL azacitidine syringes can therefore be achieved provided they are immediately frozen at –20 °C and then stored at 5 °C for 3 days. |
topic |
azacitidine stability freezing advance preparation |
url |
https://doi.org/10.1515/pthp-2016-0023 |
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