Department of Pharmacy, University of Oslo, Sem Sælands vei 3, 0371 Oslo, Norway.
Department of Pharmacy, University of Oslo, Sem Sælands vei 3, 0371 Oslo, Norway; Nanoform Finland PLC, Viikinkaari 4, 00790 Helsinki, Finland.
Eur J Pharm Sci. 2024 Jan 1;192:106619. doi: 10.1016/j.ejps.2023.106619. Epub 2023 Oct 21.
This study investigates the influence of drug load and polymer molecular weight on the structure of tablets three-dimensionally (3D) printed from the binary mixture of prednisolone and hydroxypropyl methylcellulose (HPMC). Three different HPMC grades, (AFFINISOL HPMC HME 15LV, 90 Da (HPMC 15LV); 100LV, 180 Da (HPMC 100LV); 4M, 500 Da (HPMC 4M)), which are suitable for hot-melt extrusion (HME), were used in this study. HME was used to fabricate feedstock material, i.e., filaments, at the lowest possible extrusion temperature. Filaments of the three HPMC grades were prepared to contain 2.5, 5, 10 and 20 % (w/w) prednisolone. The thermal degradation of the filaments was studied with thermogravimetric analysis, while solid-state properties of the drug-loaded filaments were assessed with the use of X-ray powder diffraction. Prednisolone in the freshly extruded filaments was determined to be amorphous for drug loads up to 10%. It remained physically stable for at least 6 months of storage, except for the filament containing 10% drug with HPMC 15LV, where recrystallization of prednisolone was detected. Fused deposition modeling was utilized to print honeycomb-shaped tablets from the HME filaments of HPMC 15LV and 100LV. The structural characteristics of the tablets were evaluated using X-ray microcomputed tomography, specifically porosity and size of structural elements were investigated. The tablets printed from HPMC 15LV possessed in general lower total porosity and pores of smaller size than tablets printed from the HPMC 100LV. The studied drug loads were shown to have minor effect on the total porosity of the tablets, though the lower the drug load was, the higher the variance of porosity along the height of the tablet was observed. It was found that tablets printed with HPMC 15LV showed higher structural similarity with the virtually designed model than tablets printed from HPMC 100LV. These findings highlight the relevance of the drug load and polymer molecular weight on the microstructure and structural properties of 3D printed tablets.
本研究考察了药物负载和聚合物分子量对从泼尼松龙和羟丙甲纤维素（HPMC）的二元混合物 3D 打印片剂结构的影响。本研究使用了三种适用于热熔挤出（HME）的不同 HPMC 等级：AFFINISOL HPMC HME 15LV，分子量为 90 Da（HPMC 15LV）；100LV，分子量为 180 Da（HPMC 100LV）；4M，分子量为 500 Da（HPMC 4M）。HME 用于在尽可能低的挤出温度下制造原料，即纤维。制备了三种 HPMC 等级的纤维，其泼尼松龙含量分别为 2.5%、5%、10%和 20%（w/w）。使用热重分析研究了纤维的热降解，同时使用 X 射线粉末衍射评估了载药纤维的固态性质。对于药物负载高达 10%的刚挤出纤维，发现泼尼松龙为无定形。在至少 6 个月的储存期内，除了含有 10%HPMC 15LV 药物的纤维外，泼尼松龙保持物理稳定，在那里检测到泼尼松龙的重结晶。利用热熔挤出纤维通过熔丝制造（FFF）打印出 HPMC 15LV 和 100LV 的蜂窝状片剂。使用 X 射线微计算机断层扫描评估了片剂的结构特征，具体研究了结构元素的孔隙率和尺寸。与由 HPMC 100LV 打印的片剂相比，由 HPMC 15LV 打印的片剂通常具有较低的总孔隙率和较小尺寸的孔。研究发现，药物负载对片剂的总孔隙率影响较小，尽管药物负载越低，片剂高度方向上的孔隙率变化越大。发现由 HPMC 15LV 打印的片剂与虚拟设计模型具有更高的结构相似性，而由 HPMC 100LV 打印的片剂则不然。这些发现强调了药物负载和聚合物分子量对 3D 打印片剂微观结构和结构性质的相关性。
