Polymorphic transitions in flufenamic acid-trehalose composites
The combination of poorly-soluble drugs with small molecule co-formers to generate amorphous solid dispersions (ASDs) has great potential to improve dissolution rate and kinetic solubility, and thus increase the bioavailability of these active ingredients. However, such ASDs are known to be unstable...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | International Journal of Pharmaceutics: X |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590156723000440 |
| _version_ | 1827878428271968256 |
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| author | Yuying Pang Simon Gaisford Oxana V. Magdysyuk Gareth R. Williams |
| author_facet | Yuying Pang Simon Gaisford Oxana V. Magdysyuk Gareth R. Williams |
| author_sort | Yuying Pang |
| collection | DOAJ |
| description | The combination of poorly-soluble drugs with small molecule co-formers to generate amorphous solid dispersions (ASDs) has great potential to improve dissolution rate and kinetic solubility, and thus increase the bioavailability of these active ingredients. However, such ASDs are known to be unstable and to crystallise upon storage or heating. In this work, we explore the crystallisation of flufenamic acid (FFA) from ASDs prepared with trehalose. FFA-trehalose mixtures were prepared at a range of w/w composition ratios, heated to melting and crash cooled to form ASDs. They were then subject to a further heat/cool cycle, which was monitored by simultaneous differential scanning calorimetry – X-ray diffraction to observe the phase changes occurring. These varied with the composition of the blend. Upon short-term storage, formulations with low trehalose contents (FFA:trehalose 5:1 w/w) recrystallised into form I FFA, while higher trehalose contents crystallised to FFA form IV. When heated, all FFA trehalose combinations ultimately recrystallised into form I before melting. Upon a second cooling cycle, systems with low trehalose content (FFA:trehalose 5:1 w/w) recrystallised into form IV, while higher trehalose contents led to FFA form I. It is thus clear that even with a single excipient it is possible to control the crystallisation pathway through judicious choice of the formulation parameters. |
| first_indexed | 2024-03-12T17:51:26Z |
| format | Article |
| id | doaj.art-50ae7bd5e7ea406384082424359ed7a7 |
| institution | Directory Open Access Journal |
| issn | 2590-1567 |
| language | English |
| last_indexed | 2024-03-12T17:51:26Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal of Pharmaceutics: X |
| spelling | doaj.art-50ae7bd5e7ea406384082424359ed7a72023-08-03T04:23:32ZengElsevierInternational Journal of Pharmaceutics: X2590-15672023-12-016100200Polymorphic transitions in flufenamic acid-trehalose compositesYuying Pang0Simon Gaisford1Oxana V. Magdysyuk2Gareth R. Williams3UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, United KingdomUCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, United KingdomDiamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE, United KingdomUCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom; Corresponding author.The combination of poorly-soluble drugs with small molecule co-formers to generate amorphous solid dispersions (ASDs) has great potential to improve dissolution rate and kinetic solubility, and thus increase the bioavailability of these active ingredients. However, such ASDs are known to be unstable and to crystallise upon storage or heating. In this work, we explore the crystallisation of flufenamic acid (FFA) from ASDs prepared with trehalose. FFA-trehalose mixtures were prepared at a range of w/w composition ratios, heated to melting and crash cooled to form ASDs. They were then subject to a further heat/cool cycle, which was monitored by simultaneous differential scanning calorimetry – X-ray diffraction to observe the phase changes occurring. These varied with the composition of the blend. Upon short-term storage, formulations with low trehalose contents (FFA:trehalose 5:1 w/w) recrystallised into form I FFA, while higher trehalose contents crystallised to FFA form IV. When heated, all FFA trehalose combinations ultimately recrystallised into form I before melting. Upon a second cooling cycle, systems with low trehalose content (FFA:trehalose 5:1 w/w) recrystallised into form IV, while higher trehalose contents led to FFA form I. It is thus clear that even with a single excipient it is possible to control the crystallisation pathway through judicious choice of the formulation parameters.http://www.sciencedirect.com/science/article/pii/S2590156723000440Solid DispersionsFlufenamic acidTrehaloseSynchrotron X-ray diffractionDifferential Scanning Calorimetry |
| spellingShingle | Yuying Pang Simon Gaisford Oxana V. Magdysyuk Gareth R. Williams Polymorphic transitions in flufenamic acid-trehalose composites International Journal of Pharmaceutics: X Solid Dispersions Flufenamic acid Trehalose Synchrotron X-ray diffraction Differential Scanning Calorimetry |
| title | Polymorphic transitions in flufenamic acid-trehalose composites |
| title_full | Polymorphic transitions in flufenamic acid-trehalose composites |
| title_fullStr | Polymorphic transitions in flufenamic acid-trehalose composites |
| title_full_unstemmed | Polymorphic transitions in flufenamic acid-trehalose composites |
| title_short | Polymorphic transitions in flufenamic acid-trehalose composites |
| title_sort | polymorphic transitions in flufenamic acid trehalose composites |
| topic | Solid Dispersions Flufenamic acid Trehalose Synchrotron X-ray diffraction Differential Scanning Calorimetry |
| url | http://www.sciencedirect.com/science/article/pii/S2590156723000440 |
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