Application of Accelerated Predictive Stability Studies in Extemporaneously Compounded Formulations of Chlorhexidine to Assess the Shelf Life
Industrially fabricated medicines have a well-defined shelf life supported by rigorous studies before their approval for commercialization. However, the shelf life of extemporaneous compounding topical formulations prepared at hospitals tends to be shorter, especially when no data are available to p...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/23/7925 |
| _version_ | 1797399775400689664 |
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| author | Olga González-González M. Paloma Ballesteros Juan J. Torrado Dolores R. Serrano |
| author_facet | Olga González-González M. Paloma Ballesteros Juan J. Torrado Dolores R. Serrano |
| author_sort | Olga González-González |
| collection | DOAJ |
| description | Industrially fabricated medicines have a well-defined shelf life supported by rigorous studies before their approval for commercialization. However, the shelf life of extemporaneous compounding topical formulations prepared at hospitals tends to be shorter, especially when no data are available to prove a longer stability period. Also, the storage conditions are unknown in many circumstances. Accelerated Predictive Stability (APS) studies have been shown to be a useful tool to predict in a faster and more accurate manner the chemical stability of extemporaneously compounded formulations requiring a minimum amount of formulation, thereby reducing the chemical drug waste per study. Shelf life will be allocated based on scientific data without compromising drug efficacy or safety. In this work, the APS approach was applied to the commercially available Cristalmina<sup>®</sup> (CR) and an extemporaneously compounded formulation of chlorhexidine (DCHX). A different degradation kinetic was found between DCHX and CR (Avrami vs. zero-order kinetics, respectively). This can explain the different shelf life described by the International Council for Harmonisation of Technical Requirements Registration Pharmaceuticals Human Use (ICH) conditions between both formulations. A predicted stability for the DCHX solution was obtained from the extrapolation of the degradation rate in long-term conditions from the Arrhenius equation. The estimated degradation from the Arrhenius equation for DCHX at 5 °C, 25 °C, and 30 °C at 365 days was 3.1%, 17.4%, and 25.9%, respectively. The predicted shelf life, in which the DCHX content was above 90%, was 26.67 months under refrigerated conditions and 5.75 and 2.24 months at 25 and 30 °C, respectively. Currently, the Spanish National Formulary recommends a shelf life of no longer than 3 months at room temperature for DCHX solution. Based on the predicted APS and confirmed by experimental long-term studies, we have demonstrated that the shelf life of DCHX extemporaneously compounded formulations could be prolonged by up to 6 months. |
| first_indexed | 2024-03-09T01:45:58Z |
| format | Article |
| id | doaj.art-66a4e462f9ea4946be1aae0460767970 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T01:45:58Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-66a4e462f9ea4946be1aae04607679702023-12-08T15:22:46ZengMDPI AGMolecules1420-30492023-12-012823792510.3390/molecules28237925Application of Accelerated Predictive Stability Studies in Extemporaneously Compounded Formulations of Chlorhexidine to Assess the Shelf LifeOlga González-González0M. Paloma Ballesteros1Juan J. Torrado2Dolores R. Serrano3Departamento de Farmacia Galénica y Tecnología Alimentaria, Facultad de Farmacia, Univsersidad Complutense de Madrid, Plaza Ramón y Cajal, s/n, 28040 Madrid, SpainDepartamento de Farmacia Galénica y Tecnología Alimentaria, Facultad de Farmacia, Univsersidad Complutense de Madrid, Plaza Ramón y Cajal, s/n, 28040 Madrid, SpainDepartamento de Farmacia Galénica y Tecnología Alimentaria, Facultad de Farmacia, Univsersidad Complutense de Madrid, Plaza Ramón y Cajal, s/n, 28040 Madrid, SpainDepartamento de Farmacia Galénica y Tecnología Alimentaria, Facultad de Farmacia, Univsersidad Complutense de Madrid, Plaza Ramón y Cajal, s/n, 28040 Madrid, SpainIndustrially fabricated medicines have a well-defined shelf life supported by rigorous studies before their approval for commercialization. However, the shelf life of extemporaneous compounding topical formulations prepared at hospitals tends to be shorter, especially when no data are available to prove a longer stability period. Also, the storage conditions are unknown in many circumstances. Accelerated Predictive Stability (APS) studies have been shown to be a useful tool to predict in a faster and more accurate manner the chemical stability of extemporaneously compounded formulations requiring a minimum amount of formulation, thereby reducing the chemical drug waste per study. Shelf life will be allocated based on scientific data without compromising drug efficacy or safety. In this work, the APS approach was applied to the commercially available Cristalmina<sup>®</sup> (CR) and an extemporaneously compounded formulation of chlorhexidine (DCHX). A different degradation kinetic was found between DCHX and CR (Avrami vs. zero-order kinetics, respectively). This can explain the different shelf life described by the International Council for Harmonisation of Technical Requirements Registration Pharmaceuticals Human Use (ICH) conditions between both formulations. A predicted stability for the DCHX solution was obtained from the extrapolation of the degradation rate in long-term conditions from the Arrhenius equation. The estimated degradation from the Arrhenius equation for DCHX at 5 °C, 25 °C, and 30 °C at 365 days was 3.1%, 17.4%, and 25.9%, respectively. The predicted shelf life, in which the DCHX content was above 90%, was 26.67 months under refrigerated conditions and 5.75 and 2.24 months at 25 and 30 °C, respectively. Currently, the Spanish National Formulary recommends a shelf life of no longer than 3 months at room temperature for DCHX solution. Based on the predicted APS and confirmed by experimental long-term studies, we have demonstrated that the shelf life of DCHX extemporaneously compounded formulations could be prolonged by up to 6 months.https://www.mdpi.com/1420-3049/28/23/7925chlorhexidinestabilityextemporaneous compoundingdegradation |
| spellingShingle | Olga González-González M. Paloma Ballesteros Juan J. Torrado Dolores R. Serrano Application of Accelerated Predictive Stability Studies in Extemporaneously Compounded Formulations of Chlorhexidine to Assess the Shelf Life Molecules chlorhexidine stability extemporaneous compounding degradation |
| title | Application of Accelerated Predictive Stability Studies in Extemporaneously Compounded Formulations of Chlorhexidine to Assess the Shelf Life |
| title_full | Application of Accelerated Predictive Stability Studies in Extemporaneously Compounded Formulations of Chlorhexidine to Assess the Shelf Life |
| title_fullStr | Application of Accelerated Predictive Stability Studies in Extemporaneously Compounded Formulations of Chlorhexidine to Assess the Shelf Life |
| title_full_unstemmed | Application of Accelerated Predictive Stability Studies in Extemporaneously Compounded Formulations of Chlorhexidine to Assess the Shelf Life |
| title_short | Application of Accelerated Predictive Stability Studies in Extemporaneously Compounded Formulations of Chlorhexidine to Assess the Shelf Life |
| title_sort | application of accelerated predictive stability studies in extemporaneously compounded formulations of chlorhexidine to assess the shelf life |
| topic | chlorhexidine stability extemporaneous compounding degradation |
| url | https://www.mdpi.com/1420-3049/28/23/7925 |
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