School of Pharmacy, University of East Anglia, Norwich, Norfolk NR4 7TJ, UK; Department of Pharmaceutical Science, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand.
School of Chemistry, University of East Anglia, Norwich, Norfolk NR4 7TJ, UK.
Int J Pharm. 2021 Jun 1;602:120637. doi: 10.1016/j.ijpharm.2021.120637. Epub 2021 Apr 24.
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, 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 E and Soluplus than with PVP and HPMCAS, and that PVP was more miscible with HPMCAS than Eudragit E 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 E 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.
通过静电纺丝（ES）将水溶性聚合物制备的难溶性药物的固体分散体纳米纤维制剂，可为口服药物给药提供显著改善的药物溶解。然而，当使用吸湿聚合物（如聚乙烯吡咯烷酮（PVP））时，环境湿度吸附会导致储存时物理稳定性差。本研究调查了使用聚合物共混物来修饰基于 PVP 的 ES 制剂模型难溶性药物非诺贝特（FF），以在不影响溶解增强的情况下改善其物理稳定性。FF-PVP ES 分散体表现出明显的溶解增强，但对高湿度的储存稳定性差。选择 PVP 与 Eudragit E、Soluplus 和醋酸琥珀酸羟丙甲纤维素（HPMCAS）的聚合物共混物，是因为这些聚合物的固有吸湿性低。药物-聚合物和聚合物-聚合物混溶性研究表明，FF 与 Eudragit E 和 Soluplus 的混溶性比与 PVP 和 HPMCAS 的混溶性高，而 PVP 与 HPMCAS 的混溶性比 Eudragit E 和 Soluplus 的混溶性高。这导致了空白纤维和载药纤维中不同的相分离构型。体外药物释放数据证实，使用 PVP-Eudragit E 保留了 PVP 制剂的溶解增强，而 PVP-Soluplus 与 FF-PVP 制剂相比降低了药物释放速率。吸湿结果证实，聚合物共混物的吸湿性降低，但相分离共混物制剂发生了制剂变形。数据揭示了理解 ES 纤维垫物理稳定性时的混溶性和相分离的重要性。研究结果为提供溶解增强与改善储存稳定性平衡的制剂设计提供了深入了解。
