Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
Eur J Pharm Sci. 2019 Mar 15;130:260-268. doi: 10.1016/j.ejps.2019.02.004. Epub 2019 Feb 5.
A realistic molecular description of amorphous drug-polymer-plasticizer matrices, suitable for the preparation of amorphous solid dispersions (ASDs) with the aid of fusion-based techniques, was evaluated. Specifically, the incorporation of two model drugs (i.e. ibuprofen, IBU, and carbamazepine, CBZ) having substantially different thermal properties and glass forming ability, on the molecular representation of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOL)/polyethylene glycol (PEG, working as a plasticizer) molecular and thermal properties were evaluated with the aid of classical molecular dynamics (MD) and docking simulations. Results showed good agreement between molecular modelling estimations and experimentally determined properties. Specifically, the computed T values that resulted from MD simulations for IBU-SOL/PEG and CBZ-SOL/PEG (53.8 and 54.2 °C, respectively) were in reasonable agreement with the corresponding values resulting from differential scanning calorimetry (DSC) measurements (49.8 and 50.1 °C), while both molecular modelling and experimental obtained results suggested miscibility among system components. Additionally, interactions between CBZ and SOL observed during MD simulations were verified by FTIR analysis, while MD simulations of the hydration process suggested strong molecular interactions between IBU-SOL and CBZ-SOL.
评估了一种适用于采用熔融技术制备无定形固体分散体（ASD）的非晶态药物-聚合物-增塑剂基质的现实分子描述。具体来说，通过经典分子动力学（MD）和对接模拟，评估了两种具有显著不同热性能和成玻璃能力的模型药物（即布洛芬（IBU）和卡马西平（CBZ））在聚己内酯-醋酸乙烯酯-聚乙二醇接枝共聚物（SOL）/聚乙二醇（PEG，用作增塑剂）分子和热性能的分子表示中的掺入。结果表明，分子建模估计与实验确定的性质之间具有良好的一致性。具体而言，MD 模拟为 IBU-SOL/PEG 和 CBZ-SOL/PEG 产生的 T 值（分别为 53.8 和 54.2°C）与差示扫描量热法（DSC）测量的相应值（49.8 和 50.1°C）相当合理，而分子建模和实验获得的结果均表明系统成分之间具有混溶性。此外，MD 模拟中观察到的 CBZ 和 SOL 之间的相互作用通过 FTIR 分析得到了验证，而 IBU-SOL 和 CBZ-SOL 水合过程的 MD 模拟表明它们之间存在强烈的分子相互作用。
