Quantification of Amlodipine Maleate Content in Amorphous Solid Dispersions Produced by Fluidized Bed Granulation Using Process Analytical Technology Tools
<b>Background:</b> Active pharmaceutical ingredient (API) content is a critical quality attribute (CQA) of amorphous solid dispersions (ASDs) prepared by spraying a solution of APIs and polymers onto the excipients in fluid bed granulator. This study presents four methods for quantifying...
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MDPI AG
2024-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/16/12/1538 |
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| author | Sandi Svetič Laura Medved Klemen Korasa Franc Vrečer |
| author_facet | Sandi Svetič Laura Medved Klemen Korasa Franc Vrečer |
| author_sort | Sandi Svetič |
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| description | <b>Background:</b> Active pharmaceutical ingredient (API) content is a critical quality attribute (CQA) of amorphous solid dispersions (ASDs) prepared by spraying a solution of APIs and polymers onto the excipients in fluid bed granulator. This study presents four methods for quantifying API content during ASD preparation. <b>Methods:</b> Raman and three near-infrared (NIR) process analysers were utilized to develop methods for API quantification. Four partial least squares (PLS) models were developed using measurements from three granulation batches, with an additional batch used to evaluate model predictability. Models performance was assessed using metrics such as root mean square error of prediction (RMSEP), root mean square error of cross-validation (RMSECV), residual prediction deviation (RPD), and others. <b>Results:</b> Off-line and at-line NIR models were identified as suitable for process control applications. Additionally, at-line Raman measurements effectively predicted the endpoint of the spraying phase. <b>Conclusions:</b> To the best of authors’ knowledge, this is the first study focused on monitoring API content during fluidized bed granulation (FBG) used for ASD preparation. The findings provide novel insights into the application of Raman and NIR process analysers with PLS modelling for monitoring and controlling ASD preparation processes. |
| format | Article |
| id | doaj-art-1a04571de8fd44768d56db433edffca8 |
| institution | Kabale University |
| issn | 1999-4923 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj-art-1a04571de8fd44768d56db433edffca82024-12-27T14:46:25ZengMDPI AGPharmaceutics1999-49232024-12-011612153810.3390/pharmaceutics16121538Quantification of Amlodipine Maleate Content in Amorphous Solid Dispersions Produced by Fluidized Bed Granulation Using Process Analytical Technology ToolsSandi Svetič0Laura Medved1Klemen Korasa2Franc Vrečer3KRKA, d. d., 8501 Novo Mesto, SloveniaKRKA, d. d., 8501 Novo Mesto, SloveniaKRKA, d. d., 8501 Novo Mesto, SloveniaFaculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia<b>Background:</b> Active pharmaceutical ingredient (API) content is a critical quality attribute (CQA) of amorphous solid dispersions (ASDs) prepared by spraying a solution of APIs and polymers onto the excipients in fluid bed granulator. This study presents four methods for quantifying API content during ASD preparation. <b>Methods:</b> Raman and three near-infrared (NIR) process analysers were utilized to develop methods for API quantification. Four partial least squares (PLS) models were developed using measurements from three granulation batches, with an additional batch used to evaluate model predictability. Models performance was assessed using metrics such as root mean square error of prediction (RMSEP), root mean square error of cross-validation (RMSECV), residual prediction deviation (RPD), and others. <b>Results:</b> Off-line and at-line NIR models were identified as suitable for process control applications. Additionally, at-line Raman measurements effectively predicted the endpoint of the spraying phase. <b>Conclusions:</b> To the best of authors’ knowledge, this is the first study focused on monitoring API content during fluidized bed granulation (FBG) used for ASD preparation. The findings provide novel insights into the application of Raman and NIR process analysers with PLS modelling for monitoring and controlling ASD preparation processes.https://www.mdpi.com/1999-4923/16/12/1538amorphous solid dispersionprocess analytical technologynear-infrared spectroscopyRaman spectroscopyfluidized bed granulationmultivariate analysis |
| spellingShingle | Sandi Svetič Laura Medved Klemen Korasa Franc Vrečer Quantification of Amlodipine Maleate Content in Amorphous Solid Dispersions Produced by Fluidized Bed Granulation Using Process Analytical Technology Tools Pharmaceutics amorphous solid dispersion process analytical technology near-infrared spectroscopy Raman spectroscopy fluidized bed granulation multivariate analysis |
| title | Quantification of Amlodipine Maleate Content in Amorphous Solid Dispersions Produced by Fluidized Bed Granulation Using Process Analytical Technology Tools |
| title_full | Quantification of Amlodipine Maleate Content in Amorphous Solid Dispersions Produced by Fluidized Bed Granulation Using Process Analytical Technology Tools |
| title_fullStr | Quantification of Amlodipine Maleate Content in Amorphous Solid Dispersions Produced by Fluidized Bed Granulation Using Process Analytical Technology Tools |
| title_full_unstemmed | Quantification of Amlodipine Maleate Content in Amorphous Solid Dispersions Produced by Fluidized Bed Granulation Using Process Analytical Technology Tools |
| title_short | Quantification of Amlodipine Maleate Content in Amorphous Solid Dispersions Produced by Fluidized Bed Granulation Using Process Analytical Technology Tools |
| title_sort | quantification of amlodipine maleate content in amorphous solid dispersions produced by fluidized bed granulation using process analytical technology tools |
| topic | amorphous solid dispersion process analytical technology near-infrared spectroscopy Raman spectroscopy fluidized bed granulation multivariate analysis |
| url | https://www.mdpi.com/1999-4923/16/12/1538 |
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