Abstract：
Minitablets are prepared using multiple die openings and multi-tip punches for greater productivity. With multiple tips on the punch barrel, the overall compaction force to be applied is commonly estimated by multiplying the desired compaction force per tip by the number of punch tips. Few researchers have however examined this proportionality and the effects of the number of punch tips and punch face geometry on the critical quality attributes (CQAs) of high drug load minitablets. In this study, the minitablets prepared by multi-tip tools exhibited greater weight variation than those prepared by single-tip tools. Their compaction was accompanied by a longer dwell time that led to a higher minitablet tensile strength and consequently a longer disintegration time. The compaction forces required to achieve a consistent set of minitablet CQAs were not directly proportional to the number of punch tips used. In comparison, the effect of punch face geometry was negligible. Increasing concentration of magnesium stearate (as lubricant) from 0.75 to 1.25 %, w/w reduced weight variation, especially of minitablets prepared by the multi-tip tools. It also increased the disintegration time but had no significant effect on the tensile strength of the minitablets regardless of type of tools used. The adjustment of compaction speed was an effective compensatory method to mitigate the differences in dwell time and tensile strength between minitablets prepared by single-tip and multi-tip standard concave tools. A larger reduction in compaction speed of the single-tip tools was required at higher compaction pressures.
摘要：
使用多个模具开口和多尖端冲头制备小片以获得更大的生产率。冲头枪管上有多个尖端，通常通过将每个尖端的期望压紧力乘以冲头尖端的数量来估计要施加的总压紧力。然而，很少有研究人员研究这种比例性以及冲头尖端数量和冲头表面几何形状对高载药量小片的关键质量属性（CQA）的影响。在这项研究中,多尖端工具制备的小片比单尖端工具制备的小片表现出更大的重量变化。它们的压实伴随着更长的停留时间，从而导致更高的小片拉伸强度，从而延长了崩解时间。实现一组一致的小型CQAs所需的压缩力与所使用的冲头尖端的数量不成正比。相比之下,冲头面几何形状的影响可以忽略不计。硬脂酸镁（作为润滑剂）的浓度从0.75％增加到1.25％，W/W减少体重变化，特别是由多尖端工具准备的小片。它也增加了崩解时间，但无论使用何种工具，对小片的拉伸强度都没有显着影响。压实速度的调整是一种有效的补偿方法，可以减轻单尖端和多尖端标准凹面工具制备的小片之间的停留时间和拉伸强度差异。在较高的压实压力下，需要较大程度地降低单尖端工具的压实速度。
