Drug-Biopolymer Dispersions: Morphology- and Temperature- Dependent (Anti)Plasticizer Effect of the Drug and Component-Specific Johari–Goldstein Relaxations
Amorphous molecule-macromolecule mixtures are ubiquitous in polymer technology and are one of the most studied routes for the development of amorphous drug formulations. For these applications it is crucial to understand how the preparation method affects the properties of the mixtures. Here, we emp...
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2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| author | Sofia Valenti Luis Javier del Valle Michela Romanini Meritxell Mitjana Jordi Puiggalí Josep Lluís Tamarit Roberto Macovez |
| author_facet | Sofia Valenti Luis Javier del Valle Michela Romanini Meritxell Mitjana Jordi Puiggalí Josep Lluís Tamarit Roberto Macovez |
| author_sort | Sofia Valenti |
| collection | DOAJ |
| description | Amorphous molecule-macromolecule mixtures are ubiquitous in polymer technology and are one of the most studied routes for the development of amorphous drug formulations. For these applications it is crucial to understand how the preparation method affects the properties of the mixtures. Here, we employ differential scanning calorimetry and broadband dielectric spectroscopy to investigate dispersions of a small-molecule drug (the Nordazepam anxiolytic) in biodegradable polylactide, both in the form of solvent-cast films and electrospun microfibres. We show that the dispersion of the same small-molecule compound can have opposite (plasticizing or antiplasticizing) effects on the segmental mobility of a biopolymer depending on preparation method, temperature, and polymer enantiomerism. We compare two different chiral forms of the polymer, namely, the enantiomeric pure, semicrystalline L-polymer (PLLA), and a random, fully amorphous copolymer containing both L and D monomers (PDLLA), both of which have lower glass transition temperature (<i>T</i><sub>g</sub>) than the drug. While the drug has a weak antiplasticizing effect on the films, consistent with its higher <i>T</i><sub>g</sub>, we find that it actually acts as a plasticizer for the PLLA microfibres, reducing their <i>T</i><sub>g</sub> by as much as 14 K at 30%-weight drug loading, namely, to a value that is lower than the <i>T</i><sub>g</sub> of fully amorphous films. The structural relaxation time of the samples similarly depends on chemical composition and morphology. Most mixtures displayed a single structural relaxation, as expected for homogeneous samples. In the PLLA microfibres, the presence of crystalline domains increases the structural relaxation time of the amorphous fraction, while the presence of the drug lowers the structural relaxation time of the (partially stretched) chains in the microfibres, increasing chain mobility well above that of the fully amorphous polymer matrix. Even fully amorphous homogeneous mixtures exhibit two distinct Johari–Goldstein relaxation processes, one for each chemical component. Our findings have important implications for the interpretation of the Johari–Goldstein process as well as for the physical stability and mechanical properties of microfibres with small-molecule additives. |
| first_indexed | 2024-03-09T20:39:09Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:39:09Z |
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| spelling | doaj.art-a21885be9deb4617bfcff00223024bda2023-11-23T23:04:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01235245610.3390/ijms23052456Drug-Biopolymer Dispersions: Morphology- and Temperature- Dependent (Anti)Plasticizer Effect of the Drug and Component-Specific Johari–Goldstein RelaxationsSofia Valenti0Luis Javier del Valle1Michela Romanini2Meritxell Mitjana3Jordi Puiggalí4Josep Lluís Tamarit5Roberto Macovez6Grup de Caracterització de Materials, Departament de Física, Universitat Politècnica de Catalunya, EEBE, Av. Eduard Maristany 10-14, E-08019 Barcelona, Catalonia, SpainSynthetic Polymers: Structure and Properties. Biodegradable Polymers, Departament de Enginyeria Química, Universitat Politècnica de Catalunya, EEBE, Av. Eduard Maristany 10-14, E-08019 Barcelona, Catalonia, SpainGrup de Caracterització de Materials, Departament de Física, Universitat Politècnica de Catalunya, EEBE, Av. Eduard Maristany 10-14, E-08019 Barcelona, Catalonia, SpainGrup de Caracterització de Materials, Departament de Física, Universitat Politècnica de Catalunya, EEBE, Av. Eduard Maristany 10-14, E-08019 Barcelona, Catalonia, SpainSynthetic Polymers: Structure and Properties. Biodegradable Polymers, Departament de Enginyeria Química, Universitat Politècnica de Catalunya, EEBE, Av. Eduard Maristany 10-14, E-08019 Barcelona, Catalonia, SpainGrup de Caracterització de Materials, Departament de Física, Universitat Politècnica de Catalunya, EEBE, Av. Eduard Maristany 10-14, E-08019 Barcelona, Catalonia, SpainGrup de Caracterització de Materials, Departament de Física, Universitat Politècnica de Catalunya, EEBE, Av. Eduard Maristany 10-14, E-08019 Barcelona, Catalonia, SpainAmorphous molecule-macromolecule mixtures are ubiquitous in polymer technology and are one of the most studied routes for the development of amorphous drug formulations. For these applications it is crucial to understand how the preparation method affects the properties of the mixtures. Here, we employ differential scanning calorimetry and broadband dielectric spectroscopy to investigate dispersions of a small-molecule drug (the Nordazepam anxiolytic) in biodegradable polylactide, both in the form of solvent-cast films and electrospun microfibres. We show that the dispersion of the same small-molecule compound can have opposite (plasticizing or antiplasticizing) effects on the segmental mobility of a biopolymer depending on preparation method, temperature, and polymer enantiomerism. We compare two different chiral forms of the polymer, namely, the enantiomeric pure, semicrystalline L-polymer (PLLA), and a random, fully amorphous copolymer containing both L and D monomers (PDLLA), both of which have lower glass transition temperature (<i>T</i><sub>g</sub>) than the drug. While the drug has a weak antiplasticizing effect on the films, consistent with its higher <i>T</i><sub>g</sub>, we find that it actually acts as a plasticizer for the PLLA microfibres, reducing their <i>T</i><sub>g</sub> by as much as 14 K at 30%-weight drug loading, namely, to a value that is lower than the <i>T</i><sub>g</sub> of fully amorphous films. The structural relaxation time of the samples similarly depends on chemical composition and morphology. Most mixtures displayed a single structural relaxation, as expected for homogeneous samples. In the PLLA microfibres, the presence of crystalline domains increases the structural relaxation time of the amorphous fraction, while the presence of the drug lowers the structural relaxation time of the (partially stretched) chains in the microfibres, increasing chain mobility well above that of the fully amorphous polymer matrix. Even fully amorphous homogeneous mixtures exhibit two distinct Johari–Goldstein relaxation processes, one for each chemical component. Our findings have important implications for the interpretation of the Johari–Goldstein process as well as for the physical stability and mechanical properties of microfibres with small-molecule additives.https://www.mdpi.com/1422-0067/23/5/2456amorphous pharmaceuticalspolymer enantiomerismValium metaboliteformulation morphologyglass transitiondielectric spectroscopy |
| spellingShingle | Sofia Valenti Luis Javier del Valle Michela Romanini Meritxell Mitjana Jordi Puiggalí Josep Lluís Tamarit Roberto Macovez Drug-Biopolymer Dispersions: Morphology- and Temperature- Dependent (Anti)Plasticizer Effect of the Drug and Component-Specific Johari–Goldstein Relaxations International Journal of Molecular Sciences amorphous pharmaceuticals polymer enantiomerism Valium metabolite formulation morphology glass transition dielectric spectroscopy |
| title | Drug-Biopolymer Dispersions: Morphology- and Temperature- Dependent (Anti)Plasticizer Effect of the Drug and Component-Specific Johari–Goldstein Relaxations |
| title_full | Drug-Biopolymer Dispersions: Morphology- and Temperature- Dependent (Anti)Plasticizer Effect of the Drug and Component-Specific Johari–Goldstein Relaxations |
| title_fullStr | Drug-Biopolymer Dispersions: Morphology- and Temperature- Dependent (Anti)Plasticizer Effect of the Drug and Component-Specific Johari–Goldstein Relaxations |
| title_full_unstemmed | Drug-Biopolymer Dispersions: Morphology- and Temperature- Dependent (Anti)Plasticizer Effect of the Drug and Component-Specific Johari–Goldstein Relaxations |
| title_short | Drug-Biopolymer Dispersions: Morphology- and Temperature- Dependent (Anti)Plasticizer Effect of the Drug and Component-Specific Johari–Goldstein Relaxations |
| title_sort | drug biopolymer dispersions morphology and temperature dependent anti plasticizer effect of the drug and component specific johari goldstein relaxations |
| topic | amorphous pharmaceuticals polymer enantiomerism Valium metabolite formulation morphology glass transition dielectric spectroscopy |
| url | https://www.mdpi.com/1422-0067/23/5/2456 |
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