Effect of drug loading and relative humidity on the mechanical properties and tableting performance of Celecoxib–PVP/VA 64 amorphous solid dispersions
Effect of drug loading and relative humidity on the mechanical properties and tableting performance of Celecoxib–PVP/VA 64 amorphous solid dispersions
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载药量和相对湿度对塞来昔布·PVP/VA 64无定形固体分散体机械性能和压片性能的影响
DOI：
10.1016/j.ijpharm.2023.123337
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发表时间：
2023
影响因子：
5.8
通讯作者：
Sun, Changquan Calvin
中科院分区：
文献类型：
--
作者：
Osei-Yeboah, Frederick;Sun, Changquan Calvin
基于聚合物的无定形固体分散体（ASD）的机械性能对相对湿度（RH）条件的变化敏感。本研究旨在了解RH对塞来昔布-聚乙烯吡咯烷酮醋酸乙烯酯共聚物（PVP/VA 64）ASD的机械性能和压片性能的影响。通过溶剂蒸发技术制备ASD以获得用于纳米压痕的膜，其也被粉碎以获得用于压实的粉末。我们的结果表明，较高的RH对应于较低的硬度H和弹性模量E。在一定的相对湿度下，E和H都随着载药量的增加而增加，达到最大值，并随着载药量的增加而降低。使用具有窄粒度范围（d50 = 9-14 µm）的ASD粉末，我们已经证明，将RH从11%增加到67%会导致纯PVP/VA 64和ASD的片剂拉伸强度提高。然而，片剂抗张强度增加的程度取决于其机械性能、HandE和载药量。在较高的压制压力和较高的相对湿度下，ASD机械性能对可压片性的影响较小，因为颗粒几乎完全变形，因此粘合面积大致相同。因此，片剂强度的差异主要由颗粒间吸引力造成。了解这些关键加工条件的影响，即，RH和压制压力将指导具有稳健可制造性的ASD片剂制剂的设计。
The mechanical properties of polymer-based amorphous solid dispersions (ASDs) are susceptible to changes in relative humidity (RH) conditions. The purpose of this study is to understand the impact of RH on both the mechanical properties and tableting performance of Celecoxib-polyvinyl pyrrolidone vinyl acetate co-polymer (PVP/VA 64) ASDs. The ASDs were prepared by solvent evaporation technique to obtain films for nanoindentation, which were also pulverized to obtain powder for compaction. Our results show that higher RH corresponds to lower Hardness,H, and Elastic Modulus,E. At a given RH, both theEandHincrease with drug loading to a maximum and decrease with further drug loading. Using ASD powders with a narrow particle size range (d50 = 9–14 µm), we have demonstrated that increasing RH from 11% to 67% leads to improved tablet tensile strength for pure PVP/VA 64 and the ASDs. However, the extent of the increase in tablet tensile strength depends on their mechanical properties,HandE, and drug loading. At a higher compaction pressure and a higher RH, the effect of ASD mechanical properties on tabletability is less because the particles are nearly fully deformed so that bonding areas are approximately the same. Thus, difference in tablet strength is mainly contributed by the inter-particulate forces of attraction. Understanding the impact of these key processing conditions, i.e., RH and compaction pressure, will guide the design of an ASD tablet formulation with robust manufacturability.