The use of polymer blends to improve stability and performance of electrospun solid dispersions: the role of miscibility and phase separation

Tipduangta, Pratchaya, Belton, Peter, McAuley, William and Qi, Sheng ORCID: (2021) The use of polymer blends to improve stability and performance of electrospun solid dispersions: the role of miscibility and phase separation. International Journal of Pharmaceutics, 602. ISSN 0378-5173

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Solid dispersion-based nanofiber formulations of poorly soluble drugs prepared by electrospinning (ES) with a water-soluble polymer, can offer significant improvements in drug dissolution for oral drug administration. However, when hygroscopic polymers, such as polyvinylpyrrolidone (PVP) are used, environmental moisture sorption can lead to poor physical stability on storage. This study investigated the use of polymer blends to modify PVP-based ES formulations of a model poorly soluble drug, fenofibrate (FF), to improve its physical stability without compromising dissolution enhancement. FF-PVP ES dispersions demonstrated clear dissolution enhancement, but poor storage stability against high humidity. Polymer blends of PVP with Eudragit E PO, Soluplus and hypromellose acetate succinate (HPMCAS), were selected because of the low intrinsic moisture sorption of these polymers. The drug-polymer and polymer-polymer miscibility study revealed that FF was more miscible with Eudragit and Soluplus than with PVP and HPMCAS, and that PVP was more miscible with HPMCAS than Eudragit and Soluplus. This led to different configurations of phase separation in the placebo and drug-loaded fibres. The in vitro drug release data confirmed that the use of PVP-Eudragit retained the dissolution enhancement of the PVP formulation, whereas PVP-Soluplus reduced the drug release rate in comparison to FF-PVP formulations. The moisture sorption results confirmed that moisture uptake by the polymer blends was reduced, but formulation deformation occurred to phase-separated blend formulations. The data revealed the importance of miscibility and phase separation in understanding the physical stability of the ES fibre mats. The findings provide insight into the design of formulations that can provide dissolution enhancement balanced with improved storage stability.

Item Type: Article
Uncontrolled Keywords: dissolution enhancement,electrospinning,moisture uptake kinetics,polymer blends,poorly soluble drugs,solid dispersion,pharmaceutical science ,/dk/atira/pure/subjectarea/asjc/3000/3003
Faculty \ School: Faculty of Science > School of Pharmacy
Faculty of Science > School of Chemistry
UEA Research Groups: Faculty of Science > Research Groups > Pharmaceutical Materials and Soft Matter
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 20 Apr 2021 23:49
Last Modified: 23 Oct 2022 02:23
DOI: 10.1016/j.ijpharm.2021.120637


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