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Pharmaceutical Prof...
Pharmaceutical Profiling and Molecular Dynamics Simulations Reveal Crystallization Effects in Amorphous Formulations
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- Edueng, Khadijah (författare)
- Uppsala universitet,Institutionen för farmaci
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- Kabedev, Aleksei (författare)
- Uppsala universitet,Institutionen för farmaci
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- Ekdahl, Alyssa (författare)
- Cockrell School of Engineering, The University of Texas at Austin, Austin, TX 78712, (USA)
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- Mahlin, Denny (författare)
- Uppsala universitet,Institutionen för farmaci,AstraZeneca Operations, Forskargatan 18, 151 85 Södertälje (Sweden)
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- Baumann, John (författare)
- Global Research and Development, Lonza, Bend, Oregon 97703, (USA)
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- Mudie, Deanna (författare)
- Global Research and Development, Lonza, Bend, Oregon 97703, (USA)
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- Bergström, Christel, 1973- (författare)
- Uppsala universitet,Institutionen för farmaci
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(creator_code:org_t)
- Elsevier, 2021
- 2021
- Engelska.
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Ingår i: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 613
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Robust and reliable in vivo performance of medicines based on amorphous solid dispersions (ASDs) depend on maintenance of physical stability and efficient supersaturation. However, molecular drivers of these two kinetic processes are poorly understood. Here we used molecular dynamics (MD) simulations coupled with experimental assessments to explore supersaturation, nucleation, and crystal growth. The effect of drug loading on physical stability and supersaturation potential was highly drug specific. Storage under humid conditions influenced crystallization, but also resulted in morphological changes and particle fusion. This led to increased particle size, which significantly reduced dissolution rate. MD simulations identified the importance of nano-compartmentalization in the crystallization rate of the ASDs. Nucleation during storage did not inherently compromise the ASD. Rather, the poorer performance resulted from a combination of properties of the compound, nanostructures formed in the formulation, and crystallization.
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
- crystallization
- drug delivery
- molecular dynamics
- physical stability
- supersaturation
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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