Biedrzycka Kinga, Marcinkowska Agnieszka
Institute of Chemical Technology and Engineering, Poznan University of Technology, Berdychowo 4, 60-965 Poznan, Poland.
Applied Manufacturing Science Sp. z o.o, Krzemowa 1, 62-002 Złotniki, Poland.
Polymers (Basel). 2023 Jun 30;15(13):2912. doi: 10.3390/polym15132912.
In this work, we report the use of the hot melt extrusion method in harsh extrusion conditions, i.e., screw rotation speed of 250 rpm, temperature above 100 °C, and two mixing zones, in order to obtain an amorphous dispersion of an active pharmaceutical ingredient (API) that is sparingly soluble in water. As a polymer matrix Eudragit EPO (E-EPO) and as an API ibuprofen (IBU) were used in the research. In addition, the plasticizer Compritol 888 ATO (COM) was tested as a factor potentially improving processing parameters and modifying the IBU release profile. In studies, 25% by weight of IBU, 10% of COM and various extrusion temperatures, i.e., 90, 100, 120, 130, and 140 °C, were used. Hot melt extrusion (HME) temperatures were selected based on the glass transition temperature of the polymer matrix (T = 42 °C) and the melting points of IBU (T = 76 °C) and COM (T = 73 °C), which were tested by differential scanning calorimetry (DSC). The thermal stability of the tested compounds, determined on the basis of measurements carried out by thermogravimetric analysis (TGA), was also taken into account. HME resulted in amorphous E-EPO/IBU solid dispersions and solid dispersions containing a partially crystalline plasticizer in the case of E-EPO/IBU/COM extrudates. Interactions between the components of the extrudate were also studied using infrared spectroscopy (FTIR-ATR). The occurrence of such interactions in the studied system, which improve the stability of the obtained solid polymer dispersions, was confirmed. On the basis of DSC thermograms and XRPD diffractograms, it was found that amorphous solid dispersions were obtained. In addition, their stability was confirmed in accelerated conditions (40 °C, 75% RH) for 28 days and 3 months. The release profiles of prepared tablets showed the release of 40% to 63% of IBU from the tablets within 180 min in artificial gastric juice solution, with the best results obtained for tablets with E-EPO/IBU extrudate prepared at a processing temperature of 140 °C.
在本研究中，我们报道了在严苛的挤出条件下使用热熔挤出法，即螺杆转速为250转/分钟、温度高于100°C以及两个混合区，以获得一种在水中溶解度低的活性药物成分（API）的无定形分散体。研究中使用了Eudragit EPO（E-EPO）作为聚合物基质，布洛芬（IBU）作为API。此外，还测试了增塑剂Compritol 888 ATO（COM）作为一种可能改善加工参数并改变IBU释放曲线的因素。在研究中，使用了25%重量的IBU、10%的COM以及各种挤出温度，即90、100、120、130和140°C。热熔挤出（HME）温度是根据聚合物基质的玻璃化转变温度（T = 42°C）以及通过差示扫描量热法（DSC）测试的IBU（T = 76°C）和COM（T = 73°C）的熔点来选择的。还考虑了通过热重分析（TGA）测量确定的测试化合物的热稳定性。HME产生了无定形的E-EPO/IBU固体分散体，对于E-EPO/IBU/COM挤出物，产生了含有部分结晶增塑剂的固体分散体。还使用红外光谱（FTIR-ATR）研究了挤出物各组分之间的相互作用。证实了在所研究的体系中存在此类相互作用，这提高了所得固体聚合物分散体的稳定性。基于DSC热谱图和XRPD衍射图，发现获得了无定形固体分散体。此外，在加速条件（40°C，75%相对湿度）下28天和3个月时证实了它们的稳定性。制备片剂的释放曲线显示，在人工胃液溶液中，180分钟内片剂中IBU的释放率为40%至63%，对于在140°C加工温度下制备的含有E-EPO/IBU挤出物的片剂，获得了最佳结果。
