Univ. Lille, CNRS, INRAE, Centrale Lille, UMR 8207 - UMET - Unité Matériaux et Transformations, F-59000, Lille, France.
Univ. Lille, CNRS, INRAE, Centrale Lille, UMR 8207 - UMET - Unité Matériaux et Transformations, F-59000, Lille, France.
Int J Pharm. 2024 Mar 25;653:123895. doi: 10.1016/j.ijpharm.2024.123895. Epub 2024 Feb 10.
Amorphous solid dispersions (ASD) are known to enhance the absorption of poorly water-soluble drugs. In this work we synthesise well-defined Polyvinylpyrrolidone (PVP) to establish the impact of dispersity and chain-end functionality on the physical properties of Curcumin (CUR)/PVP ASD. Thermodynamic characterisation of synthesised PVP emphasises a strong effect of the dispersity on the glass transition temperature (T), 50 °C higher for synthesised PVP than for commercial PVP K12 of same molar mass. This increase of T affects the thermodynamic properties of CUR/PVP ASD successfully formulated up to 70 wt% of CUR by milling or solvent evaporation. The evolution of both the T and CUR solubility values versus CUR content points out the development of fairly strong CUR-PVP interactions that strengthen the antiplasticising effect of PVP on the T of ASD. However, for ASD formulated with commercial PVP this effect is counterbalanced at low CUR content by a plasticising effect due to the shortest PVP chains. Moreover, the overlay of the phase and state diagrams highlights the strong impact of the polymer dispersity on the stability of CUR/PVP ASD. ASD formulated with low dispersity PVP are stable on larger temperature and concentration ranges than those formulated with PVP K12.
无定形固体分散体(ASD)已知可提高水溶性差的药物的吸收。在这项工作中,我们合成了具有明确结构的聚乙烯吡咯烷酮(PVP),以确定分散度和链端官能团对姜黄素(CUR)/PVP ASD 物理性质的影响。合成 PVP 的热力学特性强调了分散度对玻璃化转变温度(T)的强烈影响,比具有相同摩尔质量的商业 PVP K12 高 50°C。这种 T 的增加通过研磨或溶剂蒸发成功地影响了高达 70wt%CUR 的 CUR/PVP ASD 的热力学性质。T 和 CUR 溶解度值随 CUR 含量的变化表明,形成了相当强的 CUR-PVP 相互作用,增强了 PVP 对 ASD T 的抗塑化作用。然而,对于用商业 PVP 配制的 ASD,由于最短的 PVP 链,这种作用在 CUR 含量较低时会被塑化作用所抵消。此外,相图和状态图的叠加突出了聚合物分散度对 CUR/PVP ASD 稳定性的强烈影响。用低分散度 PVP 配制的 ASD 在更大的温度和浓度范围内比用 PVP K12 配制的 ASD 更稳定。