Development and Validation of a New Storage Procedure to Extend the In-Use Stability of Azacitidine in Pharmaceutical Formulations
Stability studies performed by the pharmaceutical industry are principally designed to fulfill licensing requirements. Thus, post-dilution or post-reconstitution stability data are frequently limited to 24 h only for bacteriological reasons, regardless of the true physicochemical stability which cou...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/9/943 |
| _version_ | 1797517649548148736 |
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| author | Antonella Iudicello Filippo Genovese Valentina Strusi Massimo Dominici Barbara Ruozi |
| author_facet | Antonella Iudicello Filippo Genovese Valentina Strusi Massimo Dominici Barbara Ruozi |
| author_sort | Antonella Iudicello |
| collection | DOAJ |
| description | Stability studies performed by the pharmaceutical industry are principally designed to fulfill licensing requirements. Thus, post-dilution or post-reconstitution stability data are frequently limited to 24 h only for bacteriological reasons, regardless of the true physicochemical stability which could, in many cases, be longer. In practice, the pharmacy-based centralized preparation may require preparation in advance for administration, for example, on weekends, holidays, or in general when pharmacies may be closed. We report an innovative strategy for storing resuspended solutions of azacitidine, a well-known chemotherapic agent, for which the manufacturer lists maximum stability of 22 h. By placing the syringe with the azacitidine reconstituted suspension between two refrigerant gel packs and storing it at 4 °C, we found that the concentration of azacitidine remained above 98% of the initial concentration for 48 h, and no change in color nor the physicochemical properties of the suspension were observed throughout the study period. The physicochemical and microbiological properties were evaluated by HPLC–UV and UHPLC-HRMS analysis, FTIR spectroscopy, pH determination, visual and subvisual examination, and sterility assay. The HPLC-UV method used for evaluating the chemical stability of azacitidine was validated according to ICH. Precise control of storage temperature was obtained by a digital data logger. Our study indicates that by changing the storage procedure of azacitidine reconstituted suspension, the usage window of the drug can be significantly extended to a time frame that better copes with its use in the clinical environment. |
| first_indexed | 2024-03-10T07:19:29Z |
| format | Article |
| id | doaj.art-a5feb349e3704fdf9e8f2a0b86ae5782 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T07:19:29Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-a5feb349e3704fdf9e8f2a0b86ae57822023-11-22T14:45:51ZengMDPI AGPharmaceuticals1424-82472021-09-0114994310.3390/ph14090943Development and Validation of a New Storage Procedure to Extend the In-Use Stability of Azacitidine in Pharmaceutical FormulationsAntonella Iudicello0Filippo Genovese1Valentina Strusi2Massimo Dominici3Barbara Ruozi4Pharmaceutical Department, Azienda USL of Modena, Largo del Pozzo 71, 41121 Modena, ItalyCentro Interdipartimentale Grandi Strumenti, University of Modena and Reggio Emilia, Via Campi 213/A, 41125 Modena, ItalyScientific and Technological Park of Medicine “Mario Veronesi”, Via 29 Maggio 6, 41037 Mirandola, ItalyScientific and Technological Park of Medicine “Mario Veronesi”, Via 29 Maggio 6, 41037 Mirandola, ItalyDepartment of Life Sciences, University of Modena and Reggio Emilia, Via Campi 213/A, 41125 Modena, ItalyStability studies performed by the pharmaceutical industry are principally designed to fulfill licensing requirements. Thus, post-dilution or post-reconstitution stability data are frequently limited to 24 h only for bacteriological reasons, regardless of the true physicochemical stability which could, in many cases, be longer. In practice, the pharmacy-based centralized preparation may require preparation in advance for administration, for example, on weekends, holidays, or in general when pharmacies may be closed. We report an innovative strategy for storing resuspended solutions of azacitidine, a well-known chemotherapic agent, for which the manufacturer lists maximum stability of 22 h. By placing the syringe with the azacitidine reconstituted suspension between two refrigerant gel packs and storing it at 4 °C, we found that the concentration of azacitidine remained above 98% of the initial concentration for 48 h, and no change in color nor the physicochemical properties of the suspension were observed throughout the study period. The physicochemical and microbiological properties were evaluated by HPLC–UV and UHPLC-HRMS analysis, FTIR spectroscopy, pH determination, visual and subvisual examination, and sterility assay. The HPLC-UV method used for evaluating the chemical stability of azacitidine was validated according to ICH. Precise control of storage temperature was obtained by a digital data logger. Our study indicates that by changing the storage procedure of azacitidine reconstituted suspension, the usage window of the drug can be significantly extended to a time frame that better copes with its use in the clinical environment.https://www.mdpi.com/1424-8247/14/9/943anticancer drugsazacitidinedrug degradationlimits of usepractical stabilityin-use stability |
| spellingShingle | Antonella Iudicello Filippo Genovese Valentina Strusi Massimo Dominici Barbara Ruozi Development and Validation of a New Storage Procedure to Extend the In-Use Stability of Azacitidine in Pharmaceutical Formulations Pharmaceuticals anticancer drugs azacitidine drug degradation limits of use practical stability in-use stability |
| title | Development and Validation of a New Storage Procedure to Extend the In-Use Stability of Azacitidine in Pharmaceutical Formulations |
| title_full | Development and Validation of a New Storage Procedure to Extend the In-Use Stability of Azacitidine in Pharmaceutical Formulations |
| title_fullStr | Development and Validation of a New Storage Procedure to Extend the In-Use Stability of Azacitidine in Pharmaceutical Formulations |
| title_full_unstemmed | Development and Validation of a New Storage Procedure to Extend the In-Use Stability of Azacitidine in Pharmaceutical Formulations |
| title_short | Development and Validation of a New Storage Procedure to Extend the In-Use Stability of Azacitidine in Pharmaceutical Formulations |
| title_sort | development and validation of a new storage procedure to extend the in use stability of azacitidine in pharmaceutical formulations |
| topic | anticancer drugs azacitidine drug degradation limits of use practical stability in-use stability |
| url | https://www.mdpi.com/1424-8247/14/9/943 |
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