Improved tableting behavior of paracetamol in the presence of polyvinylpyrrolidone additive: Effect of mixing conditions

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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.