Title :

Thinking of bosentan repurposing – A study on dehydration and amorphization

Author(s) :

Krupa, Anna [Auteur correspondant]
Uniwersytet Jagielloński w Krakowie = Jagiellonian University [UJ]
Danede, Florence [Auteur]
Unité Matériaux et Transformations - UMR 8207 [UMET]
Węgrzyn, Agnieszka [Auteur]
Uniwersytet Jagielloński w Krakowie = Jagiellonian University [UJ]
Majda, Dorota [Auteur]
Uniwersytet Jagielloński w Krakowie = Jagiellonian University [UJ]
willart, Jean-François [Auteur]
Unité Matériaux et Transformations (UMET) - UMR 8207

Journal title :

International Journal of Pharmaceutics

Volume number :

622

Pages :

121846

Publisher :

Elsevier BV

Publication date :

2022-06

ISSN :

0378-5173

English keyword(s) :

Bosentan
Vitrification
Amorphization kinetics
Ball milling
Dehydration
Dissolution

HAL domain(s) :

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]

English abstract : [en]

New clinical indications for an orphan drug bosentan are prompting the improvement of the drug formulation. Since bosentan is available as monohydrate, the information on its anhydrous form together with the assessment of ...
Show more >New clinical indications for an orphan drug bosentan are prompting the improvement of the drug formulation. Since bosentan is available as monohydrate, the information on its anhydrous form together with the assessment of its glass forming ability is necessary when developing enabling formulations. The aim of this research was, therefore, to analyze the phenomena occurring upon dehydration and amorphization of bosentan. The anhydrous form was obtained by a thermal treatment of the monohydrate and characterized for the first time using DSC and XRD. Two stable amorphous forms were prepared by cooling of the melt and high energy ball milling (Tg = 82 ⁰C). The chemical stability of milled bosentan was evaluated using ATR-IR and 1H NMR as well. The kinetics of bosentan amorphization was established. It was stated that bosentan could be easily amorphized. Importantly, even if the system was semiamorphous, there was no recrystallization while heating. The concentration–time curves recorded in biorelevant media, confirmed the beneficial effect of amorphization on the dissolution of bosentan. Yet, the amorphous form recrystallized into the monohydrate form in the gastric milieu. This phenomenon was accompanied by a reversible color change from yellow, which is typical of bosentan glass, to creamywhite that is characteristic of the crude crystalline drugShow less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CNRS
INRAE
ENSCL

Collections :

• Unité Matériaux et Transformations (UMET) - UMR 8207

Research team(s) :

Matériaux Moléculaires et Thérapeutiques

Submission date :

2022-06-24T12:42:09Z
2022-06-27T08:58:15Z
2022-06-28T12:31:49Z