Department of Pharmacy, University of Copenhagen, Universitetsparken 2, -2100, Copenhagen, DK, Denmark.
Faculty of Science and Engineering, Åbo Akademi University, Tykistökatu 6A, 20521, Turku, Finland.
Pharm Res. 2017 Dec;34(12):2689-2697. doi: 10.1007/s11095-017-2254-8. Epub 2017 Sep 19.
Many future drug products will be based on innovative manufacturing solutions, which will increase the need for a thorough understanding of the interplay between drug material properties and processability. In this study, hot melt extrusion of a drug-drug mixture with minimal amount of polymeric excipient was investigated.
Using indomethacin-cimetidine as a model drug-drug system, processability of physical mixtures with and without 5% (w/w) of polyethylene oxide (PEO) were studied using Differential Scanning Calorimetry (DSC) and Small Amplitude Oscillatory Shear (SAOS) rheometry. Extrudates containing a co-amorphous glass solution were produced and the solid-state composition of these was studied with DSC.
Rheological analysis indicated that the studied systems display viscosities higher than expected for small molecule melts and addition of PEO decreased the viscosity of the melt. Extrudates of indomethacin-cimetidine alone displayed amorphous-amorphous phase separation after 4 weeks of storage, whereas no phase separation was observed during the 16 week storage of the indomethacin-cimetidine extrudates containing 5% (w/w) PEO.
Melt extrusion of co-amorphous extrudates with low amounts of polymer was found to be a feasible manufacturing technique. Addition of 5% (w/w) polymer reduced melt viscosity and prevented phase separation.
许多未来的药物产品将基于创新的制造解决方案，这将增加对药物材料性质和可加工性之间相互作用的透彻理解的需求。在这项研究中，研究了用最小量聚合物赋形剂的药物混合物的热熔挤出。
使用吲哚美辛-西咪替丁作为药物-药物系统的模型，使用差示扫描量热法（DSC）和小振幅振荡剪切（SAOS）流变仪研究了含有和不含有 5%（w/w）聚氧化乙烯（PEO）的物理混合物的可加工性。制备了含有共无定形玻璃溶液的挤出物，并使用 DSC 研究了这些挤出物的固态组成。
流变分析表明，所研究的系统显示出高于小分子熔体预期的粘度，并且添加 PEO 降低了熔体的粘度。吲哚美辛-西咪替丁单独的挤出物在储存 4 周后显示出无定形-无定形相分离，而在储存 16 周期间，含有 5%（w/w）PEO 的吲哚美辛-西咪替丁挤出物未观察到相分离。
发现低聚合物含量的共无定形挤出物的熔融挤出是一种可行的制造技术。添加 5%（w/w）聚合物降低了熔体粘度并防止了相分离。
