Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-Indomethacin
To benefit from the optimized dissolution properties of active pharmaceutical ingredients in their amorphous forms, co-amorphisation as a viable tool to stabilize these amorphous phases is of both academic and industrial interest. Reports dealing with the physical stability and recrystallization beh...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-10-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/20/10/19571 |
| _version_ | 1819153680623992832 |
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| author | Andreas Beyer Holger Grohganz Korbinian Löbmann Thomas Rades Claudia S. Leopold |
| author_facet | Andreas Beyer Holger Grohganz Korbinian Löbmann Thomas Rades Claudia S. Leopold |
| author_sort | Andreas Beyer |
| collection | DOAJ |
| description | To benefit from the optimized dissolution properties of active pharmaceutical ingredients in their amorphous forms, co-amorphisation as a viable tool to stabilize these amorphous phases is of both academic and industrial interest. Reports dealing with the physical stability and recrystallization behavior of co-amorphous systems are however limited to qualitative evaluations based on the corresponding X-ray powder diffractograms. Therefore, the objective of the study was to develop a quantification model based on X-ray powder diffractometry (XRPD), followed by a multivariate partial least squares regression approach that enables the simultaneous determination of up to four solid state fractions: crystalline naproxen, γ-indomethacin, α-indomethacin as well as co-amorphous naproxen-indomethacin. For this purpose, a calibration set that covers the whole range of possible combinations of the four components was prepared and analyzed by XRPD. In order to test the model performances, leave-one-out cross validation was performed and revealed root mean square errors of validation between 3.11% and 3.45% for the crystalline molar fractions and 5.57% for the co-amorphous molar fraction. In summary, even four solid state phases, involving one co-amorphous phase, can be quantified with this XRPD data-based approach. |
| first_indexed | 2024-12-22T15:09:02Z |
| format | Article |
| id | doaj.art-3404fb310cc64e64ae3fff611807bff9 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-22T15:09:02Z |
| publishDate | 2015-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-3404fb310cc64e64ae3fff611807bff92022-12-21T18:21:54ZengMDPI AGMolecules1420-30492015-10-012010195711958710.3390/molecules201019571molecules201019571Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-IndomethacinAndreas Beyer0Holger Grohganz1Korbinian Löbmann2Thomas Rades3Claudia S. Leopold4Division of Pharmaceutical Technology, University of Hamburg, Hamburg 20146, GermanyDepartment of Pharmacy, University of Copenhagen, Copenhagen 2100, DenmarkDepartment of Pharmacy, University of Copenhagen, Copenhagen 2100, DenmarkDepartment of Pharmacy, University of Copenhagen, Copenhagen 2100, DenmarkDivision of Pharmaceutical Technology, University of Hamburg, Hamburg 20146, GermanyTo benefit from the optimized dissolution properties of active pharmaceutical ingredients in their amorphous forms, co-amorphisation as a viable tool to stabilize these amorphous phases is of both academic and industrial interest. Reports dealing with the physical stability and recrystallization behavior of co-amorphous systems are however limited to qualitative evaluations based on the corresponding X-ray powder diffractograms. Therefore, the objective of the study was to develop a quantification model based on X-ray powder diffractometry (XRPD), followed by a multivariate partial least squares regression approach that enables the simultaneous determination of up to four solid state fractions: crystalline naproxen, γ-indomethacin, α-indomethacin as well as co-amorphous naproxen-indomethacin. For this purpose, a calibration set that covers the whole range of possible combinations of the four components was prepared and analyzed by XRPD. In order to test the model performances, leave-one-out cross validation was performed and revealed root mean square errors of validation between 3.11% and 3.45% for the crystalline molar fractions and 5.57% for the co-amorphous molar fraction. In summary, even four solid state phases, involving one co-amorphous phase, can be quantified with this XRPD data-based approach.http://www.mdpi.com/1420-3049/20/10/19571co-amorphoussolid state analysiscompositionmultivariatePLSXRPDrecrystallizationstability |
| spellingShingle | Andreas Beyer Holger Grohganz Korbinian Löbmann Thomas Rades Claudia S. Leopold Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-Indomethacin Molecules co-amorphous solid state analysis composition multivariate PLS XRPD recrystallization stability |
| title | Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-Indomethacin |
| title_full | Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-Indomethacin |
| title_fullStr | Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-Indomethacin |
| title_full_unstemmed | Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-Indomethacin |
| title_short | Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-Indomethacin |
| title_sort | multivariate quantification of the solid state phase composition of co amorphous naproxen indomethacin |
| topic | co-amorphous solid state analysis composition multivariate PLS XRPD recrystallization stability |
| url | http://www.mdpi.com/1420-3049/20/10/19571 |
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