The University of Bradford Institutional Repository
The University of Bradford Institutional Repository
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DOI：
10.1021/mp400124z
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发表时间：
2013-09
影响因子：
4.9
通讯作者：
K. Paluch;L. Tajber;Owen I. Corrigan;A. Healy
中科院分区：
文献类型：
--
作者：
K. Paluch;L. Tajber;Owen I. Corrigan;A. Healy
为了研究使用活性药物成分的不同固态形式和比表面积（TBET）对可压片性和溶出性能的影响，将氯噻嗪钠和氯噻嗪钾（CTZK）盐的单水合和二水合结晶形式与替代的无水和无定形形式进行比较，以及通过喷雾干燥制备的具有大比表面积的氯噻嗪钠和钾的无定形微粒。对不同压片压力下制备的单组分凸形片剂的硬度、抗张强度、孔隙率和比表面积进行了表征。结果证实了压缩机制的复杂性。通常可以得出结论，固态形式（结晶与无定形）、水合类型（存在水的间隙分子、脱水物）或材料的比表面积等因素对粉末的可压片性有直接影响。观察到，对于相同固态形式的粉末，具有较大比表面积的那些粉末压实良好，并且比具有较低表面积的粉末更好，即使在相对低的压缩压力下。在较低的压缩压力下从高表面积多孔微粒制备的压块呈现最短的溶解时间，当与由等效材料制成的压块相比时，其必须在较高的压缩压力下压缩以获得令人满意的压块。因此，由纳米颗粒微粒（NPMP）组成的材料可被认为适合于直接压实，并且由于其良好的压实性能而可能作为填充剂、API、载体或粘合剂包含在片剂制剂中。
In order to investigate the effect of using different solid state forms and specific surface area (TBET) of active pharmaceutical ingredients on tabletability and dissolution performance, the mono- and dihydrated crystalline forms of chlorothiazide sodium and chlorothiazide potassium (CTZK) salts were compared to alternative anhydrous and amorphous forms, as well as to amorphous microparticles of chlorothiazide sodium and potassium which were produced by spray drying and had a large specific surface area. The tablet hardness and tensile strength, porosity, and specific surface area of single-component, convex tablets prepared at different compression pressures were characterized. Results confirmed the complexity of the compressibility mechanisms. In general it may be concluded that factors such as solid-state form (crystalline vs amorphous), type of hydration (presence of interstitial molecules of water, dehydrates), or specific surface area of the material have a direct impact on the tabletability of the powder. It was observed that, for powders of the same solid state form, those with a larger specific surface area compacted well, and better than powders of a lower surface area, even at relatively low compression pressures. Compacts prepared at lower compression pressures from high surface area porous microparticles presented the shortest times to dissolve, when compared with compacts made of equivalent materials, which had to be compressed at higher compression pressures in order to obtain satisfactory compacts. Therefore, materials composed of nanoparticulate microparticles (NPMPs) may be considered as suitable for direct compaction and possibly for inclusion in tablet formulations as bulking agents, APIs, carriers, or binders due to their good compactibility performance.