Browne Emer, Worku Zelalem A, Healy Anne Marie
SSPC The SFI Research Centre for Pharmaceuticals, School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.
Pharmaceutics. 2020 May 8;12(5):433. doi: 10.3390/pharmaceutics12050433.
When developing an amorphous solid dispersion (ASD), a prudent choice of polymer is critical to several aspects of ASD performance including: processability, solid state stability and dissolution rate. However, there is little guidance available to formulators to aid judicious polymer selection and a "trial and error" approach is often taken. This study aims to facilitate rational polymer selection and formulation design by generating ASDs using a range of poly-vinyl polymers and ketoprofen as a model active pharmaceutical ingredient (API) and evaluating several aspects of their performance. The molecular weight of the polymer and the ratio of vinyl pyrrolidone to vinyl acetate in the polymer were found to influence the relative humidity at which the relative humidity induced glass transition occurred, as well as the extent of ketoprofen supersaturation achieved during dynamic solubility testing. Interestingly, ASD tablets containing polymers with the vinyl pyrrolidone functional group exhibited higher tensile strengths than those without. This points towards the binder functionality of vinyl pyrrolidone. In conclusion, the physicochemical properties of poly-vinyl polymers greatly influence ketoprofen ASD performance and due regard should be paid to these properties in order to develop an ASD with the desired attributes.
在开发无定形固体分散体（ASD）时，谨慎选择聚合物对于ASD性能的多个方面至关重要，这些方面包括：可加工性、固态稳定性和溶解速率。然而，配方设计师在明智地选择聚合物方面几乎没有可参考的指导，通常采用“试错”方法。本研究旨在通过使用一系列聚乙烯基聚合物和酮洛芬作为模型活性药物成分（API）制备ASD，并评估其性能的多个方面，以促进合理的聚合物选择和配方设计。发现聚合物的分子量以及聚合物中乙烯基吡咯烷酮与醋酸乙烯酯的比例会影响相对湿度诱导玻璃化转变发生时的相对湿度，以及动态溶解度测试期间实现的酮洛芬过饱和度程度。有趣的是，含有具有乙烯基吡咯烷酮官能团聚合物的ASD片剂表现出比不含该官能团的片剂更高的拉伸强度。这表明了乙烯基吡咯烷酮的粘合剂功能。总之，聚乙烯基聚合物的物理化学性质极大地影响酮洛芬ASD的性能，为了开发具有所需特性的ASD，应充分考虑这些性质。
