Jones David S, Margetson Daniel N, McAllister Mark S, Andrews Gavin P
School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97, Lisburn Road, Belfast BT9 7BL, United Kingdom.
School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97, Lisburn Road, Belfast BT9 7BL, United Kingdom; GlaxoSmithKline, Pharmaceutical Development, New Frontiers Science Park, Harlow, Essex CM19 5AW, United Kingdom.
Int J Pharm. 2015 Sep 30;493(1-2):251-9. doi: 10.1016/j.ijpharm.2015.07.024. Epub 2015 Jul 15.
Given the growing interest in thermal processing methods, this study describes the use of an advanced rheological technique, capillary rheometry, to accurately determine the thermorheological properties of two pharmaceutical polymers, Eudragit E100 (E100) and hydroxypropylcellulose JF (HPC) and their blends, both in the presence and absence of a model therapeutic agent (quinine, as the base and hydrochloride salt). Furthermore, the glass transition temperatures (Tg) of the cooled extrudates produced using capillary rheometry were characterised using Dynamic Mechanical Thermal Analysis (DMTA) thereby enabling correlations to be drawn between the information derived from capillary rheometry and the glass transition properties of the extrudates. The shear viscosities of E100 and HPC (and their blends) decreased as functions of increasing temperature and shear rates, with the shear viscosity of E100 being significantly greater than that of HPC at all temperatures and shear rates. All platforms were readily processed at shear rates relevant to extrusion (approximately 200-300 s(-1)) and injection moulding (approximately 900 s(-1)). Quinine base was observed to lower the shear viscosities of E100 and E100/HPC blends during processing and the Tg of extrudates, indicative of plasticisation at processing temperatures and when cooled (i.e. in the solid state). Quinine hydrochloride (20% w/w) increased the shear viscosities of E100 and HPC and their blends during processing and did not affect the Tg of the parent polymer. However, the shear viscosities of these systems were not prohibitive to processing at shear rates relevant to extrusion and injection moulding. As the ratio of E100:HPC increased within the polymer blends the effects of quinine base on the lowering of both shear viscosity and Tg of the polymer blends increased, reflecting the greater solubility of quinine within E100. In conclusion, this study has highlighted the importance of capillary rheometry in identifying processing conditions, polymer miscibility and plasticisation phenomena.
鉴于对热加工方法的兴趣日益浓厚，本研究描述了使用一种先进的流变技术——毛细管流变仪，来准确测定两种药用聚合物（丙烯酸树脂E100（E100）和羟丙基纤维素JF（HPC））及其共混物在有无模型治疗剂（奎宁，以碱和盐酸盐形式）存在下的热流变性质。此外，使用动态热机械分析（DMTA）对通过毛细管流变仪制备的冷却挤出物的玻璃化转变温度（Tg）进行了表征，从而能够建立毛细管流变仪所得信息与挤出物玻璃化转变性质之间的相关性。E100和HPC（及其共混物）的剪切粘度随温度和剪切速率的增加而降低，在所有温度和剪切速率下，E100的剪切粘度均显著高于HPC。所有体系在与挤出（约200 - 300 s⁻¹）和注塑（约900 s⁻¹）相关的剪切速率下都易于加工。观察到奎宁碱在加工过程中会降低E100和E100/HPC共混物的剪切粘度以及挤出物的Tg，这表明在加工温度下以及冷却时（即固态）发生了增塑作用。盐酸奎宁（20% w/w）在加工过程中增加了E100和HPC及其共混物的剪切粘度，且不影响母体聚合物的Tg。然而，这些体系的剪切粘度在与挤出和注塑相关的剪切速率下并不妨碍加工。随着聚合物共混物中E100:HPC比例的增加，奎宁碱对聚合物共混物剪切粘度和Tg降低的影响增大，这反映了奎宁在E100中的溶解度更高。总之，本研究强调了毛细管流变仪在确定加工条件、聚合物相容性和增塑现象方面的重要性。
