Sökning: WFRF:(Löbmann Korbinian)
> (2024) >
Analysis of stabili...
Analysis of stabilization mechanisms in β-lactoglobulin-based amorphous solid dispersions by experimental and computational approaches
-
- Zhuo, Xuezhi (författare)
- Univ Copenhagen, Dept Pharm, DK-2100 Copenhagen, Denmark.
-
- Foderà, Vito (författare)
- Univ Copenhagen, Dept Pharm, DK-2100 Copenhagen, Denmark.
-
- Larsson, Per (författare)
- Uppsala universitet,Institutionen för farmaci
-
visa fler...
-
- Schaal, Zarah (författare)
- Univ Copenhagen, Dept Pharm, DK-2100 Copenhagen, Denmark.
-
- Bergström, Christel A. S., 1973- (författare)
- Uppsala universitet,Institutionen för farmaci
-
- Löbmann, Korbinian (författare)
- Univ Copenhagen, Dept Pharm, DK-2100 Copenhagen, Denmark.;Zerion Pharm AS, DK-3460 Birkerod, Denmark.
-
- Kabedev, Aleksei (författare)
- Uppsala universitet,Institutionen för farmaci
-
visa färre...
-
Univ Copenhagen, Dept Pharm, DK-2100 Copenhagen, Denmark Institutionen för farmaci (creator_code:org_t)
- Elsevier, 2024
- 2024
- Engelska.
-
Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier. - 0928-0987 .- 1879-0720. ; 192
- Relaterad länk:
-
https://doi.org/10.1...
-
visa fler...
-
https://uu.diva-port... (primary) (Raw object)
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Our previous work shows that β-lactoglobulin-stabilized amorphous solid dispersion (ASD) loaded with 70 % indomethacin remains stable for more than 12 months. The stability is probably due to hydrogen bond networks spread throughout the ASD, facilitated by the indomethacin which has both hydrogen donors and acceptors. To investigate the stabilization mechanisms further, here we tested five other drug molecules, including two without any hydrogen bond donors. A combination of experimental techniques (differential scanning calorimetry, X-ray power diffraction) and molecular dynamics simulations was used to find the maximum drug loadings for ASDs with furosemide, griseofulvin, ibuprofen, ketoconazole and rifaximin. This approach revealed the underlying stabilization factors and the capacity of computer simulations to predict ASD stability. We searched the ASD models for crystalline patterns, and analyzed diffusivity of the drug molecules and hydrogen bond formation. ASDs loaded with rifaximin and ketoconazole remained stable for at least 12 months, even at 90 % drug loading, whereas stable drug loadings for furosemide, griseofulvin and ibuprofen were at a maximum of 70, 50 and 40 %, respectively. Steric confinement and hydrogen bonding to the proteins were the most important stabilization mechanisms at low drug loadings (≤ 40 %). Inter-drug hydrogen bond networks (including those with induced donors), ionic interactions, and a high Tg of the drug molecule were additional factors stabilizing the ASDs at drug loading greater than 40 %.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- Amorphous solid dispersion
- Molecular dynamics
- Stability
- Poorly water-soluble drugs
- Diffusivity
- Crystalline pattern
- beta-lactoglobulin
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas