Titre :

When drugs plasticize film coatings: Unusual formulation effects observed with metoprolol and Eudragit RS

Auteur(s) :

Karrout, Youness [Auteur]
Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation - Advanced Drug Delivery Systems - U 1008 [MBLC - ADDS]
Advanced Drug Delivery Systems (ADDS) - U1008
Siepmann, Florence [Auteur]
Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation - Advanced Drug Delivery Systems - U 1008 [MBLC - ADDS]
Advanced Drug Delivery Systems (ADDS) - U1008
Benzine, Youcef [Auteur]
Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation - Advanced Drug Delivery Systems - U 1008 [MBLC - ADDS]
Advanced Drug Delivery Systems (ADDS) - U1008
Paccou, Laurent [Auteur]
Unité Matériaux et Transformations - UMR 8207 [UMET]
Guinet, Yannick [Auteur]
Unité Matériaux et Transformations - UMR 8207 [UMET]
Unité Matériaux et Transformations (UMET) - UMR 8207
Hedoux, Alain [Auteur]
Unité Matériaux et Transformations - UMR 8207 [UMET]
Unité Matériaux et Transformations (UMET) - UMR 8207
Siepmann, Juergen [Auteur]
Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation - Advanced Drug Delivery Systems - U 1008 [MBLC - ADDS]
Advanced Drug Delivery Systems (ADDS) - U1008

Titre de la revue :

International journal of pharmaceutics

Numéro :

539

Pagination :

39-49

Date de publication :

2018-03

ISSN :

0378-5173

Discipline(s) HAL :

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

Résumé en anglais : [en]

Metoprolol tartrate and metoprolol free base loaded pellet starter cores were coated with Eudragit RS, plasticized with 25% triethyl citrate (TEC). The initial drug loading and coating level were varied from 10 to 40 and ...
Lire la suite >Metoprolol tartrate and metoprolol free base loaded pellet starter cores were coated with Eudragit RS, plasticized with 25% triethyl citrate (TEC). The initial drug loading and coating level were varied from 10 to 40 and 0 to 20%, respectively. Drug release was measured in 0.1 N HCl and phosphate buffer pH 7.4. The water uptake and swelling kinetics, mechanical properties and TEC leaching of/from coated pellets and/or thin, free films of identical composition as the film coatings were monitored. The following unusual tendencies were observed: (i) the relative drug release rate from coated pellets increased with increasing initial drug content, and (ii) drug release from pellets was much faster for metoprolol free base compared to metoprolol tartrate, despite its much lower solubility (factor >70). These phenomena could be explained by plasticizing effects of the drug for the polymeric film coatings. In particular: 1) Metoprolol free base is a much more potent plasticizer for Eudragit RS than the tartrate, leading to higher film permeability and overcompensating the pronounced differences in drug solubility. Also, Raman imaging revealed that substantial amounts of the free base migrated into the film coatings, whereas this was not the case for the tartrate. 2) The plasticizing effects of the drug for the film coating overcompensated potential increasing limited solubility effects when increasing the initial drug loading from 10 to 40%. In summary, this study clearly demonstrates how important the plasticization of polymeric controlled release film coatings by drugs can be, leading to unexpected formulation effects.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CHU Lille
ENSCL
CNRS
INRA
Inserm

Collections :

• Advanced Drug Delivery Systems (ADDS) - U1008
• Unité Matériaux et Transformations (UMET) - UMR 8207

Équipe(s) de recherche :

Matériaux Moléculaires et Thérapeutiques

Date de dépôt :

2019-05-17T09:11:13Z
2021-06-23T13:16:26Z
2021-09-29T10:58:00Z
2024-04-02T13:17:19Z
2024-04-29T07:51:18Z