Title :

Bosentan monohydrate and sildenafil base as two companions in enabling formulations

Author(s) :

Strojewski, Dominik [Auteur]
Uniwersytet Jagielloński w Krakowie = Jagiellonian University [UJ]
Lalik, Sebastian [Auteur]
Uniwersytet Jagielloński w Krakowie = Jagiellonian University [UJ]
Danede, Florence [Auteur]
Unité Matériaux et Transformations - UMR 8207 [UMET]
Górska, Natalia [Auteur]
Uniwersytet Jagielloński w Krakowie = Jagiellonian University [UJ]
Deptuch, Aleksandra [Auteur]
Marzec, Monika [Auteur]
Uniwersytet Jagielloński w Krakowie = Jagiellonian University [UJ]
Willart, Jean-François [Auteur]
Unité Matériaux et Transformations (UMET) - UMR 8207
Krupa, Anna [Auteur]
Uniwersytet Jagielloński w Krakowie = Jagiellonian University [UJ]

Journal title :

International journal of pharmaceutics

Abbreviated title :

International Journal of Pharmaceutics

Volume number :

661

Pages :

124312

Publisher :

Elsevier BV

Publication date :

2024-08

ISSN :

0378-5173

English keyword(s) :

Combination drugs
Mixture drug products
Amorphous solid dispersions
Molecular alloys
Supersaturated systems
Poorly soluble drugs
Mechanical activation
High energy ball milling

HAL domain(s) :

Chimie/Matériaux
Physique [physics]/Matière Condensée [cond-mat]/Science des matériaux [cond-mat.mtrl-sci]

English abstract : [en]

Hypothesis: Sildenafil base and bosentan monohydrate are co-administered in a chronic therapy of pulmonary arterial hypertension (PAH). Both drugs are poorly soluble in water, and their bioavailability is limited to ca. ...
Show more >Hypothesis: Sildenafil base and bosentan monohydrate are co-administered in a chronic therapy of pulmonary arterial hypertension (PAH). Both drugs are poorly soluble in water, and their bioavailability is limited to ca. 50 %. Since bosentan is a weak acid, whereas sildenafil is a weak base, we assumed that their co-amorphization could: (i) improve their solubility in the gastrointestinal fluids, (ii) enable to reach supersaturation and (iii) ensure stabilization of supersaturated solutions. If successful, this could accelerate the development of new fixed-dose combination drugs. Experiments: The co-amorphous formulations were prepared using high energy ball milling. Their solid state properties were assessed using XRD, DSC, FT-MIR, and dielectric spectroscopy. Particle size distribution and surface wetting were also analyzed. Polarizing optical microscopy and scanning electron microscopy were applied to assess the microstructure of these powders. A new HPLC-DAD method was developed for a simultaneous quantification of both drugs. Findings: It was shown that binary formulations in which bosentan was molecularly dispersed in sildenafil base (Tg = 64-78 °C) could be manufactured in the high energy ball milling process. When the sildenafil load was below 50 wt. %, the formulations showed the greatest thermal stability and formed long-lasting bosentan supersaturation in PBS.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CNRS
INRAE
ENSCL

Collections :

• Unité Matériaux et Transformations (UMET) - UMR 8207

Submission date :

2024-09-05T14:40:29Z
2024-09-06T08:17:58Z