Molecular indicators of surface and bulk instability of hot melt extruded amorphous solid dispersions

Yang, Ziyi, Nollenberger, Kathrin, Albers, Jessica, Craig, Duncan and Qi, Sheng ORCID: https://orcid.org/0000-0003-1872-9572 (2015) Molecular indicators of surface and bulk instability of hot melt extruded amorphous solid dispersions. Pharmaceutical Research, 32 (4). pp. 1210-1228. ISSN 0724-8741

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Abstract

Purpose: To identify molecular indicators of bulk and surface instabilities of amorphous dispersions prepared by hot melt extrusion. Methods: Four model drugs with different physicochemical properties were formulated with EUDRAGIT® E PO using hot melt extrusion. Samples were aged under a range of conditions for up to 6 months and characterized using SEM, ATR-FTIR, PXRD and MTDSC. The effects of a range of thermodynamic, kinetic and molecular parameters, including glass transition temperature, molecular mobility, the crystallization tendency of the amorphous drug and drug-polymer miscibility, on the bulk and surface stabilities of the solid dispersions were evaluated. Results: For all drug-containing systems, a higher degree of instability was observed at the surface of the material in comparison to the bulk. Stressed humidity showed a more profound effect on the dispersions in comparison to stress temperature, reducing both their surface and bulk stabilities. For supersaturated systems the order of the bulk and surface instabilities of the samples was found following the same order of the molecular mobilities of the amorphous model drugs. This was attributed to the presence of phase separation of amorphous drug-rich domains in the supersaturated extrudates. Conclusions: The stability of the amorphous drug-rich domains appears to be governed by the physical stabilities of the amorphous drugs. The more commonly used indicators such as Tg, fragility of the amorphous drug and the theoretically predicted drug-polymer solubility showed less influence on the bulk and surface stabilities of the extrudates in comparison to the molecular mobility of the amorphous drug.

Item Type: Article
Uncontrolled Keywords: amorphous molecular dispersions,hot melt extrusion,molecular mobility,physical stability,surface crystallization
Faculty \ School: Faculty of Science > School of Pharmacy
Faculty of Science
UEA Research Groups: Faculty of Science > Research Groups > Drug Delivery and Pharmaceutical Materials (former - to 2017)
Faculty of Science > Research Groups > Pharmaceutical Materials and Soft Matter
Depositing User: Pure Connector
Date Deposited: 09 Mar 2015 07:35
Last Modified: 04 Mar 2024 17:24
URI: https://ueaeprints.uea.ac.uk/id/eprint/52550
DOI: 10.1007/s11095-014-1527-8

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