Monoclinic paracetamol (PA) is notorious as a poorly compactible model drug. Polyvinylpyrrolidone (PVP) is a polymer that can act as an effective binder to improve the mechanical properties of PA. It is surprising however that the role of mixing conditions on the physicochemical and mechanical properties of PA–PVP mixtures has not been reported previously. The results of this work showed that PA–PVP mixtures containing 5% (w/w) PVP prepared using high energy mixing conditions had considerably smaller particle size distributions and higher cohesivities than mixtures prepared using low energy mixing conditions. Solid-state analysis did not detect any change in the monoclinic crystalline form of PA after mixing with PVP. The following rank order of tabletability for PA–PVP mixtures was obtained according to the mixing condition: low shear ∼ medium shear < dry high shear < wet high shear < high-speed homogenization. A higher level of hydrogen bonding was detected in the mixtures prepared via high energy mixing conditions than in those prepared using low energy mixing conditions. Mixing is therefore a critical process that needs to be optimized during the preparation of interactive mixtures for tableting.

单斜体扑热息痛（PA）作为致密性差的模型药物而臭名昭著。聚乙烯吡咯烷酮（PVP）是一种聚合物，可以充当有效的粘合剂来改善PA的机械性能。然而令人惊讶的是，以前没有报道混合条件对PA-PVP混合物的物理化学和机械性能的作用。这项工作的结果表明，与使用低能混合条件制备的混合物相比，使用高能混合条件制备的含有5％（w / w）PVP的PA-PVP混合物具有明显更小的粒径分布和更高的内聚性。与PVP混合后，固态分析未检测到PA的单斜晶体形式有任何变化。根据混合条件，获得了以下PA-PVP混合物可压片性的等级顺序：低剪切〜中剪切<干高剪切<湿高剪切<高速均质化。在通过高能量混合条件制备的混合物中，检测到的氢键的水平高于在使用低能量混合条件制备的混合物中的氢键的水平。因此，混合是关键过程，需要在制备用于压片的交互式混合物时进行优化。