Hot melt extrusion is used in pharmacy to improve dissolution rate of poorly water-soluble active ingredients. The extrudate contains amorphous active ingredient dispersed in polymer carrier which prevents recrystallisation. Milling is a key step in the extrudate processing since it controls particle size, which has an important influence on flow properties and dissolution rate of the active ingredient from the final product.
In order to determine the appropriate milling process parameters, milling was performed on three different hammer mills. Milling was carried out on two laboratory mills, HammerWitt and FreDrive and on the production mill MFH-6. For milling used extrudate consisted of a 6:4 copolymer of vinyl pyrrolidone and vinyl acetate, Polysorbate 80 and colloidal silica. We have investigated how the type of mill, milling elements, milling speeds, mesh size and dosing speeds affect the particle size distribution, particle shape and flow properties. The particle size distribution, aspect ratio and sphericity were determined by dynamic image analysis using a Camsizer XT. The flow properties were also determined and the samples were imaged using scanning electron microscope. Three designs of experiments were prepared and the results were processed using the computer program Umetrics MODDE.
It was demonstrated that particle size is most affected by milling speed and mesh size. Higher speeds and smaller mesh openings produce smaller particles. The effect of milling speed is significant when using a mesh with larger openings. Milling speed and mesh size also impact on the particle shape. At higher milling speeds the particles are rounder and the aspect ratio is higher. The shape of the particles is also influenced by the use of different milling elements, since the use of knives results in more elongated particles. Milling process parameters also impact on the flow characteristics, which are better at lower milling speeds and larger mesh openings. It was shown that powders with larger particles have better flow properties.
Using the MODDE computer program, three models were built to determine the optimal process parameters to achieve the optimum size distribution and the appropriate flow properties.
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