Xie Tian, Taylor Lynne S
Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907.
Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907.
J Pharm Sci. 2017 Jan;106(1):100-110. doi: 10.1016/j.xphs.2016.06.017. Epub 2016 Jul 29.
The effectiveness of different polymers, alone or in combination, in inhibiting the crystallization of celecoxib (CEX) from amorphous solid dispersions (ASDs) exposed to different temperatures and relative humidities was evaluated. It was found that polyvinylpyrrolidone (PVP) and PVP-vinyl acetate formed stronger or more extensive hydrogen bonding with CEX than cellulose-based polymers. This, combined with their better effectiveness in raising the glass transition temperature (T) of the dispersions, provided better physical stabilization of amorphous CEX against crystallization in the absence of moisture when compared with dispersions formed with cellulose derivatives. In ternary dispersions containing 2 polymers, the physical stability was minimally impaired by the presence of a cellulose-based polymer when the major polymer present was PVP. On exposure to moisture, stability of the CEX ASDs was strongly affected by both the dispersion hygroscopicity and the strength of the intermolecular interactions. Binary and ternary ASDs containing PVP appeared to undergo partial amorphous-amorphous phase separation when exposed 94% relative humidity, followed by crystallization, whereas other binary ASDs crystallized directly without amorphous-amorphous phase separation.
评估了不同聚合物单独或组合使用时，对暴露于不同温度和相对湿度下的塞来昔布（CEX）无定形固体分散体（ASD）结晶的抑制效果。结果发现，聚乙烯吡咯烷酮（PVP）和聚维酮-醋酸乙烯酯与CEX形成的氢键比纤维素基聚合物更强或更广泛。这与它们在提高分散体玻璃化转变温度（T）方面更好的效果相结合，与用纤维素衍生物形成的分散体相比，在无水分情况下能为无定形CEX提供更好的抗结晶物理稳定性。在含有两种聚合物的三元分散体中，当主要聚合物为PVP时，纤维素基聚合物的存在对物理稳定性的损害最小。暴露于湿气中时，CEX ASD的稳定性受到分散体吸湿性和分子间相互作用强度的强烈影响。含有PVP的二元和三元ASD在暴露于94%相对湿度时似乎会发生部分非晶-非晶相分离，随后结晶，而其他二元ASD则直接结晶，无非晶-非晶相分离。
