Titre :

Amorphous solid dispersions of Terfenadine into PVP: insights from the molecular mobility characterisation

Auteur(s) :

Dudognon, Emeline [Auteur]
Unité Matériaux et Transformations (UMET) - UMR 8207
Bama, Jeanne Annick [Auteur]
Unité Matériaux et Transformations (UMET) - UMR 8207
Affouard, Frédéric [Auteur]
Unité Matériaux et Transformations (UMET) - UMR 8207

Titre de la manifestation scientifique :

12th Conference on Broadband Dielectric Spectroscopy and its applications BDS 2024

Ville :

Lisbon (Portugal)

Pays :

Portugal

Date de début de la manifestation scientifique :

2024-09-01

Discipline(s) HAL :

Physique [physics]/Matière Condensée [cond-mat]/Science des matériaux [cond-mat.mtrl-sci]
Physique [physics]/Matière Condensée [cond-mat]/Matière Molle [cond-mat.soft]
Physique [physics]/Matière Condensée [cond-mat]/Systèmes désordonnés et réseaux de neurones [cond-mat.dis-nn]

Résumé en anglais : [en]

Active Pharmaceutical Ingredient (API) are generally developed in the crystalline state for obvious long-term stability reasons. However, due to their increasing complexity, molecules under development show poor bio-availability ...
Lire la suite >Active Pharmaceutical Ingredient (API) are generally developed in the crystalline state for obvious long-term stability reasons. However, due to their increasing complexity, molecules under development show poor bio-availability properties resulting from a low solubility in water. To overcome this hurdle, there is a growing interest for several years in the development of amorphous solid dispersions (ASD) in which the amorphous API is dispersed in a polymeric excipient. Indeed, on the one hand, the glassy state of the API shows an enhanced bio-availability compared to the crystalline phase due to its much higher Gibbs free energy. On the other hand, the polymeric matrix hinders the re-crystallisation of the API and promote its dissolution. However, in spite of numerous studies, parameters that control the stability of these ASD are still misunderstood, especially the role played by the molecular mobility (wide amplitude or more localised motions). The aim of the presented research work is to characterise by Dielectric Relaxation Spectroscopy (DRS) the molecular mobility of mixtures of an API, Terfenadine [1], dispersed into a polymer, Polyvinylpyrrolidone PVP K12, to gain insights into the link between dynamics and thermal stability of these ASD. Co-milling at room temperature of Terfenadine (TFD) and PVP allows to formulate ASD in all the concentration range and the molecular mobility of blends with different TFD contents are deeply characterised by DRS. Results show that a slowing down of the main dynamics occurs as the content of PVP increases, which underlines its anti-plasticisation effect. Moreover, a modification of the shape of the alpha relaxation is evidenced with the development of a low-frequency component for TFD contents higher than 70 %w/w, which highlights a heterogeneity of the main dynamics. The features (VTF parameters) of both components being those of an alpha relaxation, this heterogeneity of the dynamics reveals a structural heterogeneity with the coexistence of two amorphous phases of different compositions, each characterised by its own dynamics. These results underline the sensitivity of DRS to probe such structural heterogeneities contrary to thermodynamic techniques (DSC or heat capacity spectroscopy in the glass transition temperature range) according which the blends appear as homogeneous (single glass transition, or single relaxation). Besides, this dynamic heterogeneity is observed whatever the ASD formulation process (by co-milling or quench from the melt). However, for high TFD contents, only ASD obtained by milling, re-crystallise on heating because of TFD crystalline nuclei remaining from the milling process. We took the opportunity of such behaviour to study in more details the main dynamics and the evolution of its heterogeneity under phase demixing/re-crystallisation of those blends. For different TFD contents, successive recordings at some chosen temperatures showed a complex evolution that can be rationalised by the confrontation with the phase and state diagrams of TFD and PVP blends established by DSC. References [1] E. Dudognon, J.-A. Bama and F. Affouard, Mol. Pharm., 2019, 4711-4724. doi: 10.1021/acs.molpharmaceut.9b00877; J.-A. Bama, E. Dudognon and F. Affouard, J. Phys. Chem. B, 2021, 11292-11307. doi: 10.1021/acs.jpcb.1c06087Lire moins >

Langue :

Anglais

Comité de lecture :

Non

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CNRS
INRAE
ENSCL

Collections :

• Unité Matériaux et Transformations (UMET) - UMR 8207

Équipe(s) de recherche :

Matériaux Moléculaires et Thérapeutiques

Date de dépôt :

2024-11-15T10:44:20Z
2024-11-18T11:04:43Z
2024-11-18T11:10:29Z