The University of Texas at Austin College of Pharmacy, Austin, TX, USA.
Drug Dev Ind Pharm. 2020 Dec;46(12):1971-1978. doi: 10.1080/03639045.2020.1831014. Epub 2020 Oct 22.
Plasticization, a common method of reducing the polymer melt viscosity in plastics extrusion, was investigated to improve the processability of a pharmaceutical formulation during twin-screw melt granulation. The thermolabile drug gabapentin was used as a model compound given previous work showed the benefit of preparing 80% drug loading gabapentin granules with hydroxypropyl cellulose as thermal binder. The plasticizer triethyl citrate was selected based on physicochemical compatibility with both the thermal binder and gabapentin by assessing polymer melt rheology and drug stability, respectively. Gabapentin was melt granulated at 80% drug loading with pre-plasticized binder using a co-rotating twin-screw extruder. The chemical stability and tabletability of the pre-plasticized granules were assessed to evaluate granule tabletability, drug stability, and process robustness. The granulation of gabapentin was facilitated by pre-plasticization, showing both increased granule growth and the ability to optimize processing conditions by lowering processing temperature. Pre-plasticization of thermal binder was therefore shown to be beneficial during melt granulation as a method of optimizing processing conditions while maintaining granule robustness.
增塑，一种常见的降低塑料挤出中聚合物熔体粘度的方法，被研究用于改善药物配方在双螺杆熔融造粒过程中的加工性能。热不稳定药物加巴喷丁被用作模型化合物，因为之前的工作表明，用羟丙纤维素作为热粘合剂制备 80%药物载量加巴喷丁颗粒是有益的。增塑剂柠檬酸三乙酯是根据与热粘合剂和加巴喷丁的物理化学相容性选择的，分别通过评估聚合物熔体流变性和药物稳定性来确定。使用同向旋转双螺杆挤出机，在 80%药物载量下用预增塑的粘合剂熔融造粒。评估预增塑颗粒的化学稳定性和可压性，以评估颗粒的可压性、药物稳定性和工艺稳健性。加巴喷丁的造粒通过预增塑得到促进，显示出颗粒生长的增加以及通过降低加工温度优化加工条件的能力。因此，在熔融造粒过程中，热粘合剂的预增塑被证明是有益的，它是一种优化加工条件的方法，同时保持颗粒的稳健性。
