GEA-NUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore, 117543, Singapore.
AAPS PharmSciTech. 2018 Feb;19(2):845-857. doi: 10.1208/s12249-017-0899-6. Epub 2017 Oct 10.
The compaction of multiple-unit pellet system (MUPS) is a challenging process due to the ease of coat damage under high compression pressure, thereby altering drug release rates. To overcome this, cushioning excipients are added to the tablet formulation. Excipients can be processed into pellets/granules and freeze-dried to increase their porosity and cushioning performance. However, successful formation of pellets/granules has specific requirements that limit formulation flexibility. In this study, a novel top-down approach that harnessed bulk freeze-drying milling was explored to avoid the challenges of pelletization/granulation. Aqueous dispersions containing 20%, w/w hydroxypropyl methylcellulose (HPMC), partially pregelatinised starch or polyvinylpyrrolidone alone, and with lactose (Lac) in 1:1 ratio, were freeze-dried and then milled to obtain particulate excipients for characterization and evaluation of their cushioning performance. This study demonstrated that bulk freeze-drying milling is a versatile method for developing excipients that are porous and directly compressible. The freeze-drying process modified the materials in a unique manner which could impart cushioning properties. Compared to unprocessed excipients, the freeze-dried products generally exhibited better cushioning effects. The drug release profile of drug-loaded pellets compacted with freeze-dried Lac-HPMC excipients was similar to that of the uncompacted drug-loaded pellets (f value = 51.7), indicating excellent cushioning effects. It was proposed that the specific balance of brittle and plastic nature of the freeze-dried Lac-HPMC composite conferred greater protective effect to the drug-loaded pellets, making it advantageous as a cushioning excipient.
多单位颗粒系统（MUPS）的压缩是一个具有挑战性的过程，因为在高压下很容易损坏包衣，从而改变药物释放速率。为了克服这一问题，可以向片剂配方中添加缓冲赋形剂。赋形剂可以加工成颗粒/丸剂并进行冷冻干燥，以增加其多孔性和缓冲性能。然而，成功形成颗粒/丸剂有特定的要求，限制了配方的灵活性。在这项研究中，探索了一种利用大块冷冻干燥粉碎的新颖自上而下的方法，以避免颗粒化/造粒的挑战。含有 20%（w/w）羟丙基甲基纤维素（HPMC）、部分预胶化淀粉或聚乙烯吡咯烷酮的水性分散体，以及乳糖（Lac）以 1:1 比例，进行冷冻干燥，然后粉碎，以获得颗粒状赋形剂，用于特性表征和缓冲性能评估。这项研究表明，大块冷冻干燥粉碎是一种开发多孔且可直接压缩的赋形剂的多功能方法。冷冻干燥过程以独特的方式改变了材料，可以赋予缓冲性能。与未加工的赋形剂相比，冷冻干燥产品通常表现出更好的缓冲效果。用冷冻干燥的 Lac-HPMC 赋形剂压缩的载药颗粒的药物释放曲线与未压实的载药颗粒相似（f 值=51.7），表明具有出色的缓冲效果。据推测，冷冻干燥的 Lac-HPMC 复合材料的脆性和塑性的特定平衡赋予了载药颗粒更大的保护作用，使其成为一种有优势的缓冲赋形剂。
