Impact of polymeric excipient on cocrystal formation via hot-melt extrusion and subsequent downstream processing
Impact of polymeric excipient on cocrystal formation via hot-melt extrusion and subsequent downstream processing
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DOI：
10.1016/j.ijpharm.2019.06.031
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发表时间：
2019-07-20
影响因子：
5.8
通讯作者：
Walker, Gavin
中科院分区：
文献类型：
--
作者：
Karimi-Jafari, Maryam;Ziaee, Ahmad;Walker, Gavin
药物共晶因其改变药物理化性质的潜力而受到越来越多的关注。在此，使用热熔挤出 (HME) 工艺生产了作为 BCS II 类活性药物成分 (API) 的布洛芬 (IBU) 和作为共形成剂的烟酰胺的 1:1 共晶体。研究了机筒温度和螺杆转速等工艺参数的影响。结果表明，添加聚合物赋形剂（例如 soluplus (Sol)）可通过增强 API 和共形成剂之间的相互作用来降低共结晶温度。为了研究共结晶对IBU-NIC共晶压片性能的影响，采用压实模拟器对纯IBU、IBU-NIC共晶、IBU-NIC物理混合物、IBU-NIC-Sol物理混合物和IBU-NIC-Sol共晶5种不同配方进行压片。研究了可压片性、可压实性和可压缩性。采用 IBU-NIC-Sol 共晶配方的样品在可压片性、可压实性和可压缩性方面优于所有其他配方。有趣的是，该样品甚至优于 IBU-NIC 共晶样品，这验证了赋形剂存在的有利效果。此外，溶出度测试证实，与纯 IBU 相比，不仅共晶样品的溶出度显着增加，甚至 IBU 和 NIC 的物理混合物的溶出度也显着增加。
Pharmaceutical cocrystals have gained increasing interest due to their potential to modify the physicochemical properties of drugs. Herein, a 1:1 cocrystal of ibuprofen (IBU) as a BCS class II active pharmaceutical ingredient (API) and nicotinamide as coformer was produced using a hot-melt extrusion (HME) process. The effect of process parameters such as barrel temperature and screw speed were studied. It was shown that the addition of polymeric excipient such as soluplus (Sol) decreases the cocrystallization temperature by enhancing the interaction between API and coformer. In order to study the effect of cocrystallization on the tableting properties of IBU-NIC cocrystal, 5 different formulations of pure IBU, IBU-NIC cocrystal, IBU-NIC physical mixture, IBU-NIC-Sol physical mixture and IBU-NIC-Sol cocrystal were tableted by a compaction simulator. Tabletability, compactibility and compressibility were investigated. The sample with IBU-NIC-Sol cocrystal formulation out-performed all the other formulations in terms of tabletability, compactibility and compressibility. Interestingly, this sample was even superior to the IBU-NIC cocrystal sample which verified the advantageous effect of the presence of an excipient. Moreover, dissolution test confirmed a noticeable increase in the dissolution of not only the cocrystal samples but even the physical mixtures of IBU and NIC compared with pure IBU.