Evaluation of the impact of mixing speed on the compressibility and compactibility of paracetamol-isomalt containing granules with factorial design

The aim of the present study is to evaluate the effect of a new formulation parameter on the characteristics of dosage form and manufacturing process. In our previous work the effects of isomalt and compression force on compaction and tablet properties were investigated. In this research paper the particles were agglomerated with purified water without using other binders. To set up the 33 type factorial design a new independent variable – mixing speed (X2) – was added to paracetamol:isomalt ratio in granules (X1) and to compression force during the tabletting process (X3). Each of these variables was examined at three levels to characterize their power and interactions. As granule's properties mass flow, densities and particle size were investigated. From the aspect of compression process lubrication coefficient and friction work were the evaluated response variables. As tablet characteristics tablet resistance to crushing and tensile strength were studied. The results indicated that the agglomeration process did not need any other binders to obtain granules with good quality. Moreover, the addition of mixing speed as a new independent variable was appropriate, since it had significant effect among others on the particle size distribution of the granules and on tablet characteristics. According to the results of the tablet quality tests the optimal mixing speed at granulation is needed which offers not only sufficient homogeneity of the granules but also appropriate tablet characteristics. Furthermore, the enhancing effect of isomalt on the compaction of granules and on the tablet characteristics is observed.

Graphical abstractTablets containing paracetamol and isomalt were prepared applying a new formulation parameter by wet granulation. Compression process and tablet characteristics were evaluated with 33 type factorial design. The addition of mixing speed as new independent variable was appropriate. An optimal mixing speed at granulation is crucial which offers not only enough homogeneity of the granules but also appropriate tablet characteristics.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Granulation of paracetamol and isomalt without binder. ► Optimal mixing speed offers sufficient granule size homogeneity and tablet quality. ► Isomalt improves compaction process and tablet characteristics.