粘结剂的选择是连续双螺杆湿法制粒(TSWG)的关键步骤,与分批造粒工艺相比,该材料在造粒机桶中的停留时间要短得多(2-40s)。聚乙烯醇(PVA)4-88在TSWG过程中被确定为有效的粘合剂,但是尚未研究其他PVA等级的潜力-聚合和水解度不同。因此,当前研究的目的是评估不同等级的PVA在TSWG过程中作为粘合剂的潜力。还研究了含有PVA等级的载药颗粒在流化床干燥过程中的破损和干燥行为。表征了三种PVA等级(4-88、18-88和40-88),并将它们的属性与Vandevivere等人先前研究的粘合剂进行了比较。通过主成分分析。三个粘合剂簇可以根据它们的属性来区分,其中每个簇包含PVA等级和先前研究的粘合剂。对于良好的水溶性和水不溶性配方,PVA4-88是PVA等级中最有效的粘合剂。这可以归因于其高的总表面能,低粘度,良好的亲水性和疏水性表面的润湿性,和通过水的粘合剂的良好润湿性。与以前研究的粘合剂相比,所有PVA等级在水不溶性配方中更有效,因为它们在较低的L/S比率下产生强颗粒(脆性低于30%)。这与PVA等级表面上高能位点的高分散表面能及其低表面张力有关。在流化床干燥过程中,PVA等级被证明是合适的粘合剂,由于低L/S比,对乙酰氨基酚(APAP)颗粒在短时间内干燥,可以生产高质量的颗粒。此外,没有发生减员,并获得强力片剂。基于这项研究,由于PVA在低L/S比下具有较高的粘合剂有效性,因此在双螺杆造粒过程中,PVA可能是优选的粘合剂。允许高效的下游处理。然而,工艺稳健性必须由包含的赋形剂控制,由于PVA等级在窄的L/S比范围内操作。
Binder selection is a crucial step in continuous twin-screw wet granulation (TSWG), as the material experiences a much shorter residence time (2-40 s) in the granulator barrel compared to batch-wise granulation processes. Polyvinyl alcohol (PVA) 4-88 was identified as an effective binder during TSWG, but the potential of other PVA grades-differing in polymerization and hydrolysis degree-has not yet been studied. Therefore, the aim of the current study was to evaluate the potential of different PVA grades as a binder during TSWG. The breakage and drying behavior during the fluidized bed drying of drug-loaded granules containing the PVA grades was also studied. Three PVA grades (4-88, 18-88, and 40-88) were characterized and their attributes were compared to previously investigated binders by Vandevivere et al. through principal component analysis. Three binder clusters could be distinguished according to their attributes, whereby each cluster contained a PVA grade and a previously investigated binder. PVA 4-88 was the most effective binder of the PVA grades for both a good water-soluble and water-insoluble formulation. This could be attributed to its high total surface energy, low viscosity, good wettability of hydrophilic and hydrophobic surfaces, and good wettability by water of the binder. Compared to the previously investigated binders, all PVA grades were more effective in the water-insoluble formulation, as they yielded strong granules (friability below 30%) at lower L/S-ratios. This was linked to the high dispersive surface energy of the high-energy sites on the surface of PVA grades and their low surface tension. During fluidized bed drying, PVA grades proved suitable binders, as the acetaminophen (APAP) granules were dried within a short time due to the low L/S-ratio, at which high-quality granules could be produced. In addition, no attrition occurred, and strong tablets were obtained. Based on this study, PVA could be the preferred binder during twin screw granulation due to its high binder effectiveness at a low L/S-ratio, allowing efficient downstream processing. However, process robustness must be controlled by the included excipients, as PVA grades are operating in a narrow L/S-ratio range.