New Development in Understanding Drug-Polymer Interactions in Pharmaceutical Amorphous Solid Dispersions from Solid-State Nuclear Magnetic Resonance

被引:16
作者
Pugliese, Andrea [1 ]
Tobyn, Michael [3 ]
Hawarden, Lucy E. [3 ]
Abraham, Anuji [4 ]
Blanc, Frederic [1 ,2 ]
机构
[1] Univ Liverpool, Dept Chem, Liverpool L69 7ZD, Lancashire, England
[2] Univ Liverpool, Stephenson Inst Renewable Energy, Liverpool L69 7ZF, Lancashire, England
[3] Bristol Myers Squibb, Drug Prod Dev, Bristol CH46 1QW, Gloucestershire, England
[4] Bristol Myers Squibb, Drug Prod Dev, New Brunswick, NJ 08903 USA
基金
英国工程与自然科学研究理事会;
关键词
Amorphous solid dispersions (ASDs); solid state nuclear magnetic resonance (NMR); API-polymer interactions; ASD stability; hot-melt extrusions (HMEs); spray-drying (SD); ACID-BASE INTERACTIONS; HYDROXYPROPYL METHYLCELLULOSE; INTERMOLECULAR INTERACTIONS; SUPERSATURATED SOLUTIONS; PHASE-SEPARATION; NMR ANALYSIS; SPECTROSCOPY; CRYSTALLIZATION; INDOMETHACIN; FORMULATIONS;
D O I
10.1021/acs.molpharmaceut.2c00479
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Pharmaceutical amorphous solid dispersions (ASDs) represent a widely used technology to increase the bioavailability of active pharmaceutical ingredients (APIs). ASDs are based on an amorphous API dispersed in a polymer, and their stability is driven by the presence of strong intermolecular interactions between these two species (e.g., hydrogen bond, electrostatic interactions, etc.). The understanding of these interactions at the atomic level is therefore crucial, and solid-state nuclear magnetic resonance (NMR) has demonstrated itself as a very powerful technique for probing API-polymer interactions. Other reviews have also reported exciting approaches to study the structures and dynamic properties of ASDs and largely focused on the study of API-polymer miscibility and on the identification of API-polymer interactions. Considering the increased use of NMR in the field, the aim of this Review is to specifically highlight recent experimental strategies used to identify API-polymer interactions and report promising recent examples using one-dimensional (1D) and two-dimensional (2D) experiments by exploiting the following emerging approaches of very-high magnetic field and ultrafast magic angle spinning (MAS). A range of different ASDs spanning APIs and polymers with varied structural motifs is targeted to illustrate new ways to understand the mechanism of stability of ASDs to enable the design of new dispersions.
引用
收藏
页码:3685 / 3699
页数:15
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