1. Drug-biopolymer dispersions: morphology-and temperature-dependent (anti)plasticizer effect of the drug and component-specific Johari–Goldstein relaxations
- Author
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Sofia Valenti, Luis Javier del Valle, Michela Romanini, Meritxell Mitjana, Jordi Puiggalí, Josep Lluís Tamarit, Roberto Macovez, Universitat Politècnica de Catalunya. Departament de Física, Universitat Politècnica de Catalunya. Departament d'Enginyeria Química, Universitat Politècnica de Catalunya. PSEP - Polimers Sintètics: Estructura i Propietats. Polimers Biodegradables, and Universitat Politècnica de Catalunya. GCM - Grup de Caracterització de Materials
- Subjects
Dielectric spectroscopy ,Biopolímers ,Polymers ,Impedance spectroscopy ,Espectroscòpia d'impedància ,Molecular mobility ,Catalysis ,Inorganic Chemistry ,Biopolymers ,Enginyeria química [Àrees temàtiques de la UPC] ,Plasticizers ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy ,Farmacologia molecular ,Calorimetry, Differential Scanning ,Formulation morphology ,Organic Chemistry ,Temperature ,Polymer enantiomerism ,General Medicine ,Valium metabolite ,Computer Science Applications ,Amorphous pharmaceuticals ,amorphous pharmaceuticals ,polymer enantiomerism ,formulation morphology ,glass transition ,dielectric spectroscopy ,molecular mobility ,secondary relaxations ,Secondary relaxations ,Glass transition ,Molecular pharmacology - Abstract
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 (Tg) than the drug. While the drug has a weak antiplasticizing effect on the films, consistent with its higher Tg, we find that it actually acts as a plasticizer for the PLLA microfibres, reducing their Tg by as much as 14 K at 30%-weight drug loading, namely, to a value that is lower than the Tg 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.
- Published
- 2022