Abstract：
Mini-tablets (MTs) with losartan potassium were developed to treat the rare disease Epidermolysis Bullosa. The focus was placed on transfer and scale-up of a direct compressible formulation from the compaction simulator STYL\'One Evo (CS) to the rotary tablet press Korsch XM 12 (RP). Transfer of tabletability and compactibility profiles from CS to RP did not show good agreement, e.g. at a tableting pressure of 125 MPa mean tensile strengths (TS) of 4 MPa on CS and 1-1.5 MPa on RP were reached. These results highlight the impact of the feed frame on final product qualities depending on process and material factors. In the scale-up studies the critical quality attributes (CQAs) mass variation, content uniformity, TS and disintegration time were investigated. After an appropriate run-up time, most CQAs reached a plateau, after reaching a balance between influx, efflux and distribution of lubricant in the feed frame. TS values of 1-2 MPa, disintegration times of max. 50 s, mass variation of 0.9-2.2 % (CV) and acceptance values below 15.0 were reached depending on chosen process parameters.
摘要：
开发了含有氯沙坦钾的微型片剂（MT）来治疗罕见疾病大疱性表皮松解症。重点放在从压实模拟器STYL'OneEvo（CS）到旋转压片机KorschXM12（RP）的直接可压缩制剂的转移和放大。从CS到RP的可压性和可压实性配置文件的转移未显示良好的一致性，例如,在125MPa的压片压力下,CS上的平均拉伸强度(TS)达到4MPa,RP上达到1-1.5MPa。这些结果突出了进料框架对最终产品质量的影响，具体取决于工艺和材料因素。在放大研究中，关键质量属性(CQA)质量变化，含量均匀性，研究了TS和崩解时间。在适当的运行时间之后，大多数CQA达到了一个平台，在达到流入之间的平衡之后，进料框架中润滑剂的流出和分布。1-2MPa的TS值，最大的崩解时间。50s,根据所选择的工艺参数，质量变化为0.9-2.2％（CV），接受值低于15.0。
