Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
Laboratory of Pharmaceutical Technology, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
Pharm Res. 2017 Nov;34(11):2312-2321. doi: 10.1007/s11095-017-2239-7. Epub 2017 Aug 15.
The aim of this study was to investigate (i) the influence of drug solid-state (crystalline or dissolved in the polymer matrix) on the melt viscosity and (ii) the influence of the drug concentration, temperature and shear rate on polymer crystallization using rheological tests.
Poly (ethylene oxide) (PEO) (100.000 g/mol) and physical mixtures (PM) containing 10-20-30-40% (w/w) ketoprofen or 10% (w/w) theophylline in PEO were rheologically characterized. Rheological tests were performed (frequency and temperature sweeps in oscillatory shear as well as shear-induced crystallization experiments) to obtain a thorough understanding of the flow behaviour and crystallization of PEO-drug dispersions.
Theophylline did not dissolve in PEO as the complex viscosity (η*) of the drug-polymer mixture increased as compared to that of neat PEO. In contrast, ketoprofen dissolved in PEO and acted as a plasticizer, decreasing η*. Acting as a nucleating agent, theophylline induced the crystallization of PEO upon cooling from the melt. On the other hand, ketoprofen inhibited crystallization upon cooling. Moreover, higher concentrations of ketoprofen in the drug-polymer mixture increasingly inhibited polymer crystallization. However, shear-induced crystallization was observed for all tested mixtures containing ketoprofen.
The obtained rheological results are relevant for understanding and predicting HME processability (e.g., barrel temperature selection) and downstream processing such as injection moulding (e.g., mold temperature selection).
本研究旨在探讨（i）药物的固体状态（结晶或溶解在聚合物基质中）对熔体粘度的影响，以及（ii）药物浓度、温度和剪切率对使用流变学测试的聚合物结晶的影响。
对聚环氧乙烷（PEO）（100.000 g/mol）和含有 10-20-30-40%（w/w）酮洛芬或 10%（w/w）茶碱的物理混合物（PM）进行了流变特性分析。进行了流变学测试（在振荡剪切中的频率和温度扫描以及剪切诱导结晶实验），以深入了解 PEO-药物分散体的流动行为和结晶。
茶碱未溶解在 PEO 中，因为药物-聚合物混合物的复合粘度（η*）比纯 PEO 的复合粘度增加。相比之下，酮洛芬溶解在 PEO 中，起到了塑化剂的作用，降低了 η*。茶碱作为成核剂，在从熔体冷却时诱导 PEO 结晶。另一方面，酮洛芬在冷却时抑制结晶。此外，药物-聚合物混合物中较高浓度的酮洛芬越来越抑制聚合物结晶。然而，所有含酮洛芬的测试混合物都观察到了剪切诱导结晶。
所获得的流变学结果对于理解和预测热机械加工（例如，机筒温度选择）以及下游加工（例如，注塑成型（例如，模具温度选择））是相关的。
